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Cancer and Metastasis Reviews
Erschienen in:

10.01.2021 | Non-Thematic Review

An overview of genetic mutations and epigenetic signatures in the course of pancreatic cancer progression

verfasst von: Aamir Ali Khan, Xinhui Liu, Xinlong Yan, Muhammad Tahir, Sakhawat Ali, Hua Huang

Erschienen in: Cancer and Metastasis Reviews | Ausgabe 1/2021

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Abstract

Pancreatic cancer (PC) is assumed to be an intimidating and deadly malignancy due to being the leading cause of cancer-led mortality, predominantly affecting males of older age. The overall (5 years) survival rate of PC is less than 9% and is anticipated to be aggravated in the future due to the lack of molecular acquaintance and diagnostic tools for its early detection. Multiple factors are involved in the course of PC development, including genetics, cigarette smoking, alcohol, family history, and aberrant epigenetic signatures of the epigenome. In this review, we will mainly focus on the genetic mutations and epigenetic signature of PC. Multiple tumor suppressor and oncogene mutations are involved in PC initiation, including K-RAS, p53, CDKN2A, and SMAD4. The mutational frequency of these genes ranges from 50 to 98% in PC. The nature of mutation diagnosis is mostly homozygous deletion, point mutation, and aberrant methylation. In addition to genetic modification, epigenetic alterations particularly aberrant hypermethylation and hypomethylation also predispose patients to PC. Hypermethylation is mostly involved in the downregulation of tumor suppressor genes and leads to PC, while multiple genes also represent a hypomethylation status in PC. Several renewable drugs and detection tools have been developed to cope with this aggressive malady, but all are futile, and surgical resection remains the only choice for prolonged survival if diagnosed before metastasis. However, the available therapeutic development is insufficient to cure PC. Therefore, novel approaches are a prerequisite to elucidating the genetic and epigenetic mechanisms underlying PC progression for healthier lifelong survival.
Literatur
1.
Siegel, R. L., Miller, K. D., & Jemal, A. (2019). Cancer statistics, 2019. CA: a Cancer Journal for Clinicians, 69, 7–34.2.
2.
Street W. Cancer Facts & Figures 2019. American Cancer Society: Atlanta, GA, USA. 2019. (Accessed on 19-11-2019).
3.
Rahib, L., Smith, B. D., Aizenberg, R., Rosenzweig, A. B., Fleshman, J. M., & Matrisian, L. M. (2014). Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Research, 74(11), 2913–2921.PubMedCrossRef
4.
Parkin, D. M., Bray, F., Ferlay, J., & Pisani, P. (2005). Global cancer statistics, 2002. CA: a Cancer Journal for Clinicians, 55(2), 74–108.
5.
Teague, A., Lim, K. H., & Wang-Gillam, A. (2015). Advanced pancreatic adenocarcinoma: a review of current treatment strategies and developing therapies. Therapeutic Advances in Medical Oncology., 7(2), 68–84.PubMedPubMedCentralCrossRef
6.
Niess, H., Kleespies, A., Andrassy, J., Pratschke, S., Angele, M. K., Guba, M., Jauch, K. W., & Bruns, C. J. (2013). Pancreatic cancer in the elderly: guidelines and individualized therapy. Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen., 84(4), 291–295.PubMed
7.
Oberstein, P. E., & Olive, K. P. (2013). Pancreatic cancer: why is it so hard to treat? Therapeutic Advances in Gastroenterology, 6(4), 321–337.PubMedPubMedCentralCrossRef
8.
Neoptolemos, J. P., Stocken, D. D., Friess, H., Bassi, C., Dunn, J. A., Hickey, H., Beger, H., Fernandez-Cruz, L., Dervenis, C., Lacaine, F., & Falconi, M. (2004). A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. The New England Journal of Medicine, 350(12), 1200–1210.PubMedCrossRef
9.
Bosetti, C., Lucenteforte, E., Silverman, D. T., Petersen, G., Bracci, P. M., Ji, B. T., Negri, E., Li, D., Risch, H. A., Olson, S. H., & Gallinger, S. (2011). Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4). Annals of Oncology, 23(7), 1880–1888.PubMedPubMedCentralCrossRef
10.
Klein, A. P., Brune, K. A., Petersen, G. M., Goggins, M., Tersmette, A. C., Offerhaus, G. J., Griffin, C., Cameron, J. L., Yeo, C. J., Kern, S., & Hruban, R. H. (2004). Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Research, 64(7), 2634–2638.PubMedCrossRef
11.
Hidalgo, M., Cascinu, S., Kleeff, J., Labianca, R., Löhr, J. M., Neoptolemos, J., Real, F. X., Van Laethem, J. L., & Heinemann, V. (2015). Addressing the challenges of pancreatic cancer: future directions for improving outcomes. Pancreatology., 15(1), 8–18.PubMedCrossRef
12.
Stewart BW, Wild CP (2019). World cancer report, 2014. Public Health.
13.
De La Cruz, M. S., Young, A. P., & Ruffin, M. T. (2014). Diagnosis and management of pancreatic cancer. American Family Physician, 89(8), 626–632.
14.
15.
Rawla, P., Sunkara, T., & Gaduputi, V. (2019). Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World Journal of Oncology., 10(1), 10.PubMedPubMedCentralCrossRef
16.
Siegel, R. L., Miller, K. D., & Jemal, A. (2016). Cancer statistics, 2016. CA: a Cancer Journal for Clinicians, 66(1), 7–30.
17.
Mohammed, S., George Van Buren, I. I., & Fisher, W. E. (2014). Pancreatic cancer: advances in treatment. World journal of gastroenterology: WJG, 20(28), 9354.PubMedPubMedCentral
18.
Haqq, J., Howells, L. M., Garcea, G., Metcalfe, M. S., Steward, W. P., & Dennison, A. R. (2014). Pancreatic stellate cells and pancreas cancer: current perspectives and future strategies. European Journal of Cancer, 50, 2570–2582.PubMedCrossRef
19.
Ikenaga, N., Ohuchida, K., Mizumoto, K., Cui, L., Kayashima, T., Morimatsu, K., et al. (2010). CD10+ pancreatic stellate cells enhance the progression of pancreatic cancer. Gastroenterology, 139, 1041–1051.PubMedCrossRef
20.
Lonardo, E., Frias-Aldeguer, J., Hermann, P. C., & Heeschen, C. (2012). Pancreatic stellate cells form a niche for cancer stem cells and promote their self-renewal and invasiveness. Cell Cycle, 11, 1282–1290.PubMedCrossRef
21.
Jacobetz, M. A., Chan, D. S., Neesse, A., Bapiro, T. E., Cook, N., Frese, K. K., et al. (2013). Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut, 62, 112–120.PubMedCrossRef
22.
Özdemir, B. C., Pentcheva-Hoang, T., Carstens, J. L., Zheng, X., Wu, C. C., Simson, T., et al. (2014). Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with diminished survival. Cancer Cell, 25, 719–734.PubMedPubMedCentralCrossRef
23.
Rhim, A. D., Oberstein, P. E., Thomas, D. H., Mirek, E. T., Palermo, C. F., Sastra, S. A., et al. (2014). Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell, 25, 735–747.PubMedPubMedCentralCrossRef
24.
Puleo, F., Nicolle, R., Blum, Y., Cros, J., Marisa, L., Demetter, P., et al. (2018). Stratification of pancreatic ductal adenocarcinomas based on tumor and microenvironment features. Gastroenterology, 155, 1999–2013.PubMedCrossRef
25.
Moffitt, R. A., Marayati, R., Flate, E. L., Volmar, K. E., Loeza, S. G., Hoadley, K. A., et al. (2015). Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nature Genetics, 47, 1168–1178.PubMedPubMedCentralCrossRef
26.
Ye, C., Zheng, L., & Yuan, C. H. (2019). Pancreatic ductal adenocarcinoma immune microenvironment and immunotherapy prospects. Zhonghua wai ke za zhi [Chinese Journal of Surgery]., 57(1), 10–15.PubMed
27.
Banerjee, K., Kumar, S., Ross, K. A., et al. (2018). Emerging trends in the immunotherapy of pancreatic cancer. Cancer Letters, 417, 35–46.PubMedCrossRef
28.
Yarchoan, M., Hopkins, A., & Jaffee, E. M. (2017). Tumor mutational burden and response rate to PD-1 inhibition. The New England Journal of Medicine, 377, 2500–2501.PubMedPubMedCentralCrossRef
29.
Laklai, H., Miroshnikova, Y. A., Pickup, M. W., et al. (2016). Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression. Nature Medicine, 22, 497.PubMedPubMedCentralCrossRef
30.
Feig, C., Gopinathan, A., Neesse, A., Chan, D. S., Cook, N., & Tuveson, D. A. (2012). The pancreas cancer microenvironment. AACR: In.CrossRef
31.
Ferdek, P. E., & Jakubowska, M. A. (2017). Biology of pancreatic stellate cellsdmore than just pancreatic cancer. Pflügers Archiv - European Journal of Physiology, 469, 1039–1050.PubMedPubMedCentralCrossRef
32.
Apte, M., Pirola, R., & Wilson, J. (2012). Pancreatic stellate cells: a starring role in normal and diseased pancreas. Frontiers in Physiology, 3, 344.PubMedPubMedCentralCrossRef
33.
Jiang, H., Hegde, S., & DeNardo, D. G. (2017). Tumor-associated fibrosis as a regulator of tumor immunity and response to immunotherapy. Cancer Immunology, Immunotherapy, 66, 1037–1048.PubMedCrossRef
34.
Pothula, S. P., Xu, Z., Goldstein, D., Pirola, R. C., Wilson, J. S., & Apte, M. V. (2016). Key role of pancreatic stellate cells in pancreatic cancer. Cancer Letters, 381, 194–200.PubMedCrossRef
35.
Von Ahrens, D., Bhagat, T. D., Nagrath, D., Maitra, A., & Verma, A. (2017). The role of stromal cancer-associated fibroblasts in pancreatic cancer. Journal of Hematology & Oncology, 10, 76.CrossRef
36.
Ohlund, D., Handly-Santana, A., Biffi, G., et al. (2017). Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. The Journal of Experimental Medicine, 214, 579–596.PubMedPubMedCentralCrossRef
37.
Ozdemir, B. C., Pentcheva-Hoang, T., Carstens, J. L., et al. (2014). Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell, 25, 719–734.PubMedPubMedCentralCrossRef
38.
Ugel, S., De Sanctis, F., Mandruzzato, S., & Bronte, V. (2015). Tumor-induced myeloid deviation: when myeloid-derived suppressor cells meet tumor-associated macrophages. Journal of Clinical Investigation, 125, 3365–3376.CrossRef
39.
Porembka, M. R., Mitchem, J. B., Belt, B. A., et al. (2012). Pancreatic adenocarcinoma induces bone marrow mobilization of myeloidderived suppressor cells which promote primary tumor growth. Cancer Immunology, Immunotherapy, 61, 1373–1385.PubMedCrossRef
40.
Stromnes, I. M., Brockenbrough, J. S., Izeradjene, K., et al. (2014). Targeted depletion of an MDSC subset unmasks pancreatic ductal adenocarcinoma to adaptive immunity. Gut., 63, 1769–1781.PubMedCrossRef
41.
Liu, G., Bi, Y., Shen, B., et al. (2014). SIRT1 limits the function and fate of myeloid-derived suppressor cells in tumors by orchestrating HIF-1aedependent glycolysis. Cancer Research, 74, 727–737.PubMedCrossRef
42.
Stromnes, I. M., Hulbert, A., Pierce, R. H., Greenberg, P. D., & Hingorani, S. R. (2017). T-cell localization, activation, and clonal expansion in human pancreatic ductal adenocarcinoma. Cancer Immunology Research, 5, 978–991.PubMedPubMedCentralCrossRef
43.
44.
Shi, C., Daniels, J. A., & Hruban, R. H. (2008). Molecular characterization of pancreatic neoplasms. Advances in Anatomic Pathology, 15(4), 185–195.PubMedCrossRef
45.
46.
Solomon, S., Das, S., Brand, R., & Whitcomb, D. C. (2012). Inherited pancreatic cancer syndromes. Cancer Journal, 18(6), 485491.CrossRef
47.
Hahn, S. A., Greenhalf, B., Ellis, I., Sina-Frey, M., Rieder, H., Korte, B., Gerdes, B., Kress, R., Ziegler, A., Raeburn, J. A., & Campra, D. (2003). BRCA2 germline mutations in familial pancreatic carcinoma. Journal of the National Cancer Institute, 95(3), 214–221.PubMedCrossRef
48.
Couch, F. J., Johnson, M. R., Rabe, K. G., Brune, K., De Andrade, M., Goggins, M., Rothenmund, H., Gallinger, S., Klein, A., Petersen, G. M., & Hruban, R. H. (2007). The prevalence of BRCA2 mutations in familial pancreatic cancer. Cancer Epidemiology and Prevention Biomarkers., 16(2), 342–346.CrossRef
49.
Murphy, K. M., Brune, K. A., Griffin, C., Sollenberger, J. E., Petersen, G. M., Bansal, R., Hruban, R. H., & Kern, S. E. (2002). Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17%. Cancer Research, 62(13), 3789–3793.PubMed
50.
Jones, S., Hruban, R. H., Kamiyama, M., Borges, M., Zhang, X., Parsons, D. W., Lin, J. C., Palmisano, E., Brune, K., Jaffee, E. M., & Iacobuzio-Donahue, C. A. (2009). Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science., 324(5924), 217.PubMedPubMedCentralCrossRef
51.
Tischkowitz, M. D., Sabbaghian, N., Hamel, N., Borgida, A., Rosner, C., Taherian, N., Srivastava, A., Holter, S., Rothenmund, H., Ghadirian, P., & Foulkes, W. D. (2009). Analysis of the gene coding for the BRCA2-interacting protein PALB2 in familial and sporadic pancreatic cancer. Gastroenterology., 137(3), 1183–1186.PubMedCrossRef
52.
Slater, E. P., Langer, P., Niemczyk, E., Strauch, K., Butler, J., Habbe, N., Neoptolemos, J. P., Greenhalf, W., & Bartsch, D. K. (2010). PALB2 mutations in European familial pancreatic cancer families. Clinical Genetics, 78(5), 490–494.PubMedCrossRef
53.
Hwang, R. F., Gordon, E. M., Anderson, W. F., & Parekh, D. (1998). Gene therapy for primary and metastatic pancreatic cancer with intraperitoneal retroviral vector bearing the wild-type p53 gene. Surgery, 124, 143–150.PubMedCrossRef
54.
Schutte, M., Hruban, R. H., Geradts, J., Maynard, R., Hilgers, W., Rabindran, S. K., Moskaluk, C. A., Hahn, S. A., Schwarte-Waldhoff, I., Schmiegel, W., et al. (1997). Abrogation of the RB/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Research, 57, 3126–3130.PubMed
55.
Blackford, A., Serrano, O. K., Wolfgang, C. L., Parmigiani, G., Jones, S., Zhang, X., Parsons, D. W., Lin, J. C., Leary, R. J., Eshleman, J. R., & Goggins, M. (2009). SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer. Clinical Cancer Research, 15(14), 4674–4679.PubMedPubMedCentralCrossRef
56.
Kim, S. T., Lim, D. H., Jang, K. T., Lim, T., Lee, J., Choi, Y. L., Jang, H. L., Yi, J. H., Baek, K. K., Park, S. H., & Park, Y. S. (2011). Impact of KRAS mutations on clinical outcomes in pancreatic cancer patients treated with first-line gemcitabine-based chemotherapy. Molecular Cancer Therapeutics, 10(10), 1993–1999.PubMedCrossRef
57.
De Bosscher, K., Hill, C. S., & Nicolas, F. J. (2004). Molecular and functional consequences of SMAD4 c-terminal missense mutations in colorectal tumour cells. The Biochemical Journal, 379, 209–216.PubMedPubMedCentralCrossRef
58.
Blackford, A., Serrano, O. K., Wolfgang, C. L., Parmigiani, G., Jones, S., Zhang, X., Parsons, D. W., Lin, J. C., Leary, R. J., Eshleman, J. R., et al. (2009). SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer. Clinical Cancer Research, 15, 4674–4679.PubMedPubMedCentralCrossRef
59.
Schutte, M., Hruban, R. H., Geradts, J., Maynard, R., Hilgers, W., Rabindran, S. K., Moskaluk, C. A., Hahn, S. A., Schwarte-Waldhoff, I., Schmiegel, W., et al. (1997). Abrogation of the RB/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Research, 57, 3126–3130.PubMed
60.
Chen, J., Li, D., Killary, A. M., Sen, S., Amos, C. I., Evans, D. B., Abbruzzese, J. L., & Frazier, M. L. (2009). Polymorphisms of p16, p27, p73, and MDM2 modulate response and survival of pancreatic cancer patients treated with preoperative chemoradiation. Annals of Surgical Oncology, 16, 431–439.PubMedCrossRef
61.
Hwang, R. F., Gordon, E. M., Anderson, W. F., & Parekh, D. (1998). Gene therapy for primary and metastatic pancreatic cancer with intraperitoneal retroviral vector bearing the wild-type p53 gene. Surgery, 124, 143–150.PubMedCrossRef
62.
Kern, S. E., Pietenpol, J. A., Thiagalingam, S., Seymour, A., Kinzler, K. W., & Vogelstein, B. (1992). Oncogenic forms of p53 inhibit p53-regulated gene expression. Science, 256, 827–830.PubMedCrossRef
63.
Bamford, S., Dawson, E., Forbes, S., Clements, J., Pettett, R., Dogan, A., Flanagan, A., Teague, J., Futreal, P. A., Stratton, M. R., et al. (2004). Thecosmic (catalogue of somatic mutations in cancer) database and website. British Journal of Cancer, 91, 355–358.PubMedPubMedCentralCrossRef
64.
Kim, S. T., Lim, D. H., Jang, K. T., Lim, T., Lee, J., Choi, Y. L., Jang, H. L., Yi, J. H., Baek, K. K., Park, S. H., et al. (2011). Impact of KRAS mutations on clinical outcomes in pancreatic cancer patients treated with first-line gemcitabine-based chemotherapy. Molecular Cancer Therapeutics, 10, 1993–1999.PubMedCrossRef
65.
Fernandez-Medarde, E., & Santos. (2011). Ras in cancer and developmental diseases. Genes & Cancer, 2, 344–358.CrossRef
66.
67.
Tites, E. C. S., & Chandran, K. S. R. (2009). A systems perspective of ras signaling in cancer. Clinical Cancer Research, 15, 1510–1513.CrossRef
68.
Forbes, S. A., Bindal, N., Bamford, S., Cole, C., Kok, C. Y., Beare, D., Jia, M., Shepherd, R., Leung, K., Menzies, A., Teague, J. W., Campbell, P. J., Stratton, M. R., & Futreal, P. A. (2011). COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Research, 39, D945–D950.PubMedCrossRef
69.
Jones, S., Zhang, X., Parsons, D. W., et al. (2008). Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science., 321(5897), 1801–1806.PubMedPubMedCentralCrossRef
70.
Hruban, R. H., van Mansfeld, A. D., Offerhaus, G. J., et al. (1993). K-ras oncogene activation in adenocarcinoma of the human pancreas: a study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridization. The American Journal of Pathology, 143(2), 545–554.PubMedPubMedCentral
71.
Caldas, S. A., Hahn, R. H., Hruban, M. S., & Redston, C. J. (1994). Detection of K-ras mutations in the stool of patients with pancreatic adenocarcinoma and pancreatic ductal hyperplasia. Cancer Research, 54, 3568–3573.PubMed
72.
Kim, J., Reber, H. A., Dry, S. M., Elashoff, D., Chen, S. L., Umetani, N., Kitago, M., Hines, O. J., Kazanjian, K. K., Hiramatsu, S., Bilchik, A. J., Yong, S., Shoup, M., & Hoon, D. S. (2006). Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins. Gut, 55, 1598–1605.PubMedPubMedCentralCrossRef
73.
Kawesha, A., Ghaneh, P., Andren-Sandberg, A., Ograed, D., Skar, R., Dawiskiba, S., Evans, J. D., Campbell, F., Lemoine, N., & Neoptolemos, J. P. (2000). K-ras oncogene subtype mutations are associated with survival but not expression of p53 p16(INK4A), p21(WAF-1), cyclin D1, erbB-2 and erbB-3 in resected pancreatic ductal adenocarcinoma. International Journal of Cancer, 89, 469–474.PubMedCrossRef
74.
RM, Ferrone, C. R., Mullarky, E., Shyh-Chang, N., Kang, Y., Fleming, J. B., Bardeesy, N., Asara, J. M., Haigis, M. C., De Pinho, R. A., Cantley, L. C., & Kimmelman, A. C. (2013). Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature, 496, 101–105.CrossRef
75.
Kawesha, A., Ghaneh, P., Andren-Sandberg, A., Ograed, D., Skar, R., Dawiskiba, S., Evans, J. D., Campbell, F., Lemoine, N., & Neoptolemos, J. P. (2000). K-ras oncogene subtype mutations are associated with survival but not expression of p53 p16(INK4A), p21(WAF-1), cyclin D1, erbB-2 and erbB-3 in resected pancreatic ductal adenocarcinoma. International Journal of Cancer, 89, 469–474.PubMedCrossRef
76.
Immervoll, H., Hoem, D., Kugarajh, K., Steine, S. J., & Molven, A. (2006). Molecular analysis of the EGFR-RAS-RAF pathway in pancreatic ductal adenocarcinomas: lack of mutations in the BRAF and EGFR genes. Virchows Archiv, 448, 788–796.PubMedCrossRef
77.
Chen, H., Tu, H., Meng, Z. Q., Chen, Z., Wang, P., & Liu, L. M. (2010). K-ras mutational status predicts poor prognosis in unresectable pancreatic cancer. European Journal of Surgical Oncology, 36, 657–662.PubMedCrossRef
78.
Reza, J., Almodovar, A. J., Srivastava, M., Veldhuis, P. P., Patel, S., Fanaian, N. I., Zhu, X., Litherland, S. A., & Arnoletti, J. P. (2019). K-RAS mutant gene found in pancreatic juice activated chromatin from peri-ampullary adenocarcinomas. Epigenetics Insights., 12, 2516865719828348.PubMedPubMedCentralCrossRef
79.
Glorieux, C., & Huang, P. (2019). Regulation of CD137 expression through K-Ras signalling in pancreatic cancer cells. Cancer Communications, 39(1), 41.PubMedPubMedCentralCrossRef
80.
Nishizawa, N., Kumamoto, Y., Katoh, H., Ushiku, H., Yokoi, K., Tanaka, T., Ishii, S., Igarashi, K., Tajima, H., Kaizu, T., & Yoshida, T. (2019). Dissected peripancreatic tissue margin is a critical prognostic factor and is associated with a K-ras gene mutation in pancreatic ductal adenocarcinoma. Oncology Letters, 17(2), 2141–2150.PubMed
81.
Adjei, A. A. (2001). Blocking oncogenic Ras signaling for cancer therapy. Journal of the National Cancer Institute, 93, 1062–1074.PubMedCrossRef
82.
Martin, N. E., Brunner, T. B., Kiel, K. D., DeLaney, T. F., Regine, W. F., Mohiuddin, M., Rosato, E. F., Haller, D. G., Stevenson, J. P., Smith, D., Pramanik, B., Tepper, J., Tanaka, W. K., Morrison, B., Deutsch, P., Gupta, A. K., Muschel, R. J., McKenna, W. G., Bernhard, E. J., & Hahn, S. M. (2004). A phase I trial of the dual farnesyltransferase and geranylgeranyltransferase inhibitor L-778,123 and radiotherapy for locally advanced pancreatic cancer. Clinical Cancer Research, 10, 5447–5454.PubMedCrossRef
83.
Chao, M. W., Chang, L. H., Tu, H. J., Chang, C. D., Lai, M. J., Chen, Y. Y., Liou, J. P., Teng, C. M., & Pan, S. L. (2019). Combination treatment strategy for pancreatic cancer involving the novel HDAC inhibitor MPT0E028 with a MEK inhibitor beyond K-Ras status. Clinical Epigenetics, 11(1), 85.PubMedPubMedCentralCrossRef
84.
Dent, P., Booth, L., Roberts, J. L., Liu, J., Poklepovic, A., Lalani, A. S., Tuveson, D., Martinez, J., & Hancock, J. F. (2019). Neratinib inhibits Hippo/YAP signaling, reduces mutant K-RAS expression, and kills pancreatic and blood cancer cells. Oncogene., 38(30), 5890–5904.PubMedPubMedCentralCrossRef
85.
86.
Jay, G., Khoury, G., DeLeo, A. B., Dippold, W. G., & Old, L. J. (1981). p53 transformation-related protein: detection of an associated phosphotransferase activity. Proceedings of the National Academy of Sciences, 78(5), 2932–2936.CrossRef
87.
Oren, M. (2003). Decision making by p53: life, death and cancer. Cell Death and Differentiation, 10(4), 431.PubMedCrossRef
88.
Vogelstein, B., Lane, D., & Levine, A. J. (2000). Surfing the p53 network. Nature., 408(6810), 307.PubMedCrossRef
89.
El-Deiry, W. S., Kern, S. E., Pietenpol, J. A., Kinzler, K. W., & Vogelstein, B. (1992). Definition of a consensus binding site for p53. Nature Genetics, 1(1), 45.PubMedCrossRef
90.
Li, M., He, Y., Dubois, W., Wu, X., Shi, J., & Huang, J. (2012). Distinct regulatory mechanisms and functions for p53-activated and p53-repressed DNA damage response genes in embryonic stem cells. Molecular Cell, 46(1), 30–42.PubMedPubMedCentralCrossRef
91.
Waldman, T., Kinzler, K. W., & Vogelstein, B. (1995). p21 is necessary for the p53-mediated G1 arrest in human cancer cells. Cancer Research, 55(22), 5187–5190.PubMed
92.
Polyak, K., Xia, Y., Zweier, J. L., Kinzler, K. W., & Vogelstein, B. (1997). A model for p53-induced apoptosis. Nature., 389(6648), 300.PubMedCrossRef
93.
Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery Jr., C. A., Butel, J. S., & Bradley, A. (1992). Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature., 356(6366), 215.PubMedCrossRef
94.
Ruggeri, B., Zhang, S., Caamano, J., et al. (1992). Human pancreatic carcinomas and cell lines reveal frequent and multiple alterations in the p53 and Rb-1 tumor suppressor genes. Oncogene, 7(8), 1503–1511.PubMed
95.
Birch, J. M., Alston, R. D., McNally, R., et al. (2001). Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene, 20(34), 4621–4628.PubMedCrossRef
96.
Casey, G., Yamanaka, Y., Friess, H., et al. (1993). p53 mutations are common in pancreatic cancer and are absent in chronic pancreatitis. Cancer Letters, 69(3), 151–160.PubMedCrossRef
97.
DiGiuseppe, J. A., Hruban, R. H., Goodman, S. N., Polak, M., Van Den Berg, F. M., Allison, D. C., Cameron, J. L., Johan, A., & Offerhaus, G. (1994). Overexpression of p53 protein in adenocarcinoma of the pancreas. American Journal of Clinical Pathology, 101(6), 684–688.PubMedCrossRef
98.
Redston, M. S., Caldas, C., Seymour, A. B., Hruban, R. H., Da Costa, L., Yeo, C. J., & Kern, S. E. (1994). p53 mutations in pancreatic carcinoma and evidence of common involvement of homocopolymer tracts in DNA microdeletions. Cancer Research, 54(11), 3025–3033.PubMed
99.
Casey, G., Yamanaka, Y., Friess, H., Kobrin, M. S., Lopez, M. E., Buchler, M., Beger, H. G., & Korc, M. (1993). p53 mutations are common in pancreatic cancer and are absent in chronic pancreatitis. Cancer Letters, 69(3), 151–160.PubMedCrossRef
100.
Izetti, P., Hautefeuille, A., Abujamra, A. L., et al. (2014). PRIMA-1, a mutant p53 reactivator, induces apoptosis and enhances chemotherapeutic cytotoxicity in pancreatic cancer cell lines. Investigational New Drugs, 32(5), 783–794.PubMedCrossRef
101.
Azmi, A. S., Philip, P. A., Wang, Z., et al. (2010). Reactivation of p53 by novel MDM2 inhibitors: implications for pancreatic cancer therapy. Current Cancer Drug Targets, 10(3), 319.PubMedPubMedCentralCrossRef
102.
Mello, S. S., Valente, L. J., Raj, N., Seoane, J. A., Flowers, B. M., McClendon, J., Bieging-Rolett, K. T., Lee, J., Ivanochko, D., Kozak, M. M., & Chang, D. T. (2017). A p53 super-tumor suppressor reveals a tumor suppressive p53-Ptpn14-Yap axis in pancreatic cancer. Cancer Cell, 32(4), 460–473.PubMedPubMedCentralCrossRef
103.
Delma, C. R., Thirugnanasambandan, S., Srinivasan, G. P., Raviprakash, N., Manna, S. K., Natarajan, M., & Aravindan, N. (2019). Fucoidan from marine brown algae attenuates pancreatic cancer progression by regulating p53–NFκB crosstalk. Phytochemistry., 167, 112078.PubMedCrossRef
104.
Cheng, J., Okolotowicz, K. J., Ryan, D., Mose, E., Lowy, A. M., & Cashman, J. R. (2019). Inhibition of invasive pancreatic cancer: restoring cell apoptosis by activating mitochondrial p53. American Journal of Cancer Research, 9(2), 390.PubMedPubMedCentral
105.
Long, J., Liu, Z., & Hui, L. (2019). Anti-tumor effect and mechanistic study of elemene on pancreatic carcinoma. BMC Complementary and Alternative Medicine, 19(1), 133.PubMedPubMedCentralCrossRef
106.
Stott, F. J., Bates, S., James, M. C., et al. (1998). The alternative product from the human CDKN2a locus, p14 (ARF), participates in a regulatory feedback loop with p53 and MDM2. The EMBO Journal, 17, 5001–5014.PubMedPubMedCentralCrossRef
107.
Serrano, M., Hannon, G. J., & Beach, D. (1993). A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature, 366(6456), 704–707.PubMedCrossRef
108.
Liggett Jr., W. H., & Sidransky, D. (1998). Role of the p16 tumor suppressor gene in cancer. Journal of Clinical Oncology, 16(3), 1197–1206.PubMedCrossRef
109.
Stott, F. J., Bates, S., James, M. C., McConnell, B. B., Starborg, M., Brookes, S., Palmero, I., Ryan, K., Hara, E., Vousden, K. H., & Peters, G. (1998). The alternative product from the human CDKN2A locus, p14ARF, participates in a regulatory feedback loop with p53 and MDM2. The EMBO Journal., 17(17), 5001–5014.PubMedPubMedCentralCrossRef
110.
Fukushima, N., Sato, N., Ueki, T., Rosty, C., Walter, K. M., Wilentz, R. E., Yeo, C. J., Hruban, R. H., & Goggins, M. (2002). Aberrant methylation of preproenkephalin and p16 genes in pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma. The American Journal of Pathology., 160(5), 1573–1581.PubMedPubMedCentralCrossRef
111.
Gerdes, B., Ramaswamy, A., Kersting, M., Ernst, M., Lang, S., Schuermann, M., Wild, A., & Bartsch, D. K. (2001). p16INK4a alterations in chronic pancreatitis—indicator for high-risk lesions for pancreatic cancer. Surgery., 129(4), 490–497.PubMedCrossRef
112.
Schutte, M., Hruban, R. H., Geradts, J., Maynard, R., Hilgers, W., Rabindran, S. K., Moskaluk, C. A., Hahn, S. A., Schwarte-Waldhoff, I., Schmiegel, W., & Baylin, S. B. (1997). Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Research, 57(15), 3126–3130.PubMed
113.
Chen, J., Li, D., Killary, A. M., Sen, S., Amos, C. I., Evans, D. B., Abbruzzese, J. L., & Frazier, M. L. (2009). Polymorphisms of p16, p27, p73, and MDM2 modulate response and survival of pancreatic cancer patients treated with preoperative chemoradiation. Annals of Surgical Oncology, 16(2), 431.PubMedCrossRef
114.
Attri, J., Srinivasan, R., Majumdar, S., Radotra, B. D., & Wig, J. (2005). Alterations of tumor suppressor gene p16 INK4a in pancreatic ductal carcinoma. BMC Gastroenterology, 5(1), 22.PubMedPubMedCentralCrossRef
115.
Loukopoulos, P., Kanetaka, K., Takamura, M., Shibata, T., Sakamoto, M., & Hirohashi, S. (2004). Orthotopic transplantation models of pancreatic adenocarcinoma derived from cell lines and primary tumors and displaying varying metastatic activity. Pancreas., 29(3), 193–203.PubMedCrossRef
116.
Klump, B., Hsieh, C. J., Nehls, O., Dette, S., Holzmann, K., Kiesslich, R., Jung, M., Sinn, U., Ortner, M., Porschen, R., & Gregor, M. (2003). Methylation status of p14ARF and p16INK4a as detected in pancreatic secretions. British Journal of Cancer, 88(2), 217.PubMedPubMedCentralCrossRef
117.
Heilmann, A. M., Perera, R. M., Ecker, V., Nicolay, B. N., Bardeesy, N., Benes, C. H., & Dyson, N. J. (2014). CDK4/6 and IGF1 receptor inhibitors synergize to suppress the growth of p16INK4A-deficient pancreatic cancers. Cancer Research, 74(14), 3947–3958.PubMedPubMedCentralCrossRef
118.
Heilmann, A. M., Perera, R. M., Ecker, V., Nicolay, B. N., Bardeesy, N., Benes, C. H., & Dyson, N. J. (2014). CDK4/6 and IGF1 receptor inhibitors synergize to suppress the growth of p16INK4A-deficient pancreatic cancers. Cancer Research, 74(14), 3947–3958.PubMedPubMedCentralCrossRef
119.
Al Baghdadi, T., Halabi, S., Garrett-Mayer, E., Mangat, P. K., Ahn, E. R., Sahai, V., Alvarez, R. H., Kim, E. S., Yost, K. J., Rygiel, A. L., & Antonelli, K. R. (2019). Palbociclib in patients with pancreatic and biliary cancer with CDKN2A alterations: results from the Targeted Agent and Profiling Utilization Registry Study. JCO Precision Oncology, 14.
120.
Hahn, S. A., Schutte, M., Hoque, A. S., Moskaluk, C. A., Da Costa, L. T., Rozenblum, E., Weinstein, C. L., Fischer, A., Yeo, C. J., Hruban, R. H., & Kern, S. E. (1996). DPC4, a candidate tumor suppressor gene at human chromosome 18q21. 1. Science., 271(5247), 350–353.PubMedCrossRef
121.
Massagué, J. (1996). TGFβ signaling: receptors, transducers, and Mad proteins. Cell., 85(7), 947–950.PubMedCrossRef
122.
Saiki, Y., & Horii, A. (2014). Molecular pathology of pancreatic cancer. Pathology International, 64(1), 10–19.PubMedCrossRef
123.
Derynck, R., Akhurst, R. J., & Balmain, A. (2001). TGF-β signaling in tumor suppression and cancer progression. Nature Genetics, 29(2), 117.PubMedCrossRef
124.
Shi, Y., & Massagué, J. (2003). Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell, 113(6), 685–700.PubMedCrossRef
125.
Evan, G. I., & Vousden, K. H. (2001). Proliferation, cell cycle and apoptosis in cancer. Nature, 411(6835), 342.PubMedCrossRef
126.
Lecanda, J., Ganapathy, V., D’Aquino-Ardalan, C., Evans, B., Cadacio, C., Ayala, A., & Gold, L. I. (2009). TGFβ prevents proteasomal degradation of the cyclin-dependent kinase inhibitor p27kip1 for cell cycle arrest. Cell Cycle, 8(5), 742–756.PubMedCrossRef
127.
Massagué, J., Blain, S. W., & Lo, R. S. (2000). TGFβ signaling in growth control, cancer, and heritable disorders. Cell., 103(2), 295–309.PubMedCrossRef
128.
De Bosscher, K., Hill, C. S., & Nicolás, F. J. (2004). Molecular and functional consequences of Smad4 C-terminal missense mutations in colorectal tumour cells. The Biochemical Journal, 379(1), 209–216.PubMedPubMedCentralCrossRef
129.
Blackford, A., Serrano, O. K., Wolfgang, C. L., Parmigiani, G., Jones, S., Zhang, X., Parsons, D. W., Lin, J. C., Leary, R. J., Eshleman, J. R., & Goggins, M. (2009). SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer. Clinical Cancer Research, 15(14), 4674–4679.PubMedPubMedCentralCrossRef
130.
Singh, P., Srinivasan, R., & Wig, J. D. (2012). SMAD4 genetic alterations predict a worse prognosis in patients with pancreatic ductal adenocarcinoma. Pancreas., 41(4), 541–546.PubMedCrossRef
131.
Hayashi, H., Kohno, T., Ueno, H., Hiraoka, N., Kondo, S., Saito, M., Shimada, Y., Ichikawa, H., Kato, M., Shibata, T., et al. (2017). Utility of assessing the number of mutated KRAS, CDKN2A, Tp53, and SMAD4 genes using a targeted deep sequencing assay as a prognostic biomarker for pancreatic cancer. Pancreas, 46, 335–340.PubMedCrossRef
132.
Wang, J. D., Jin, K., Chen, X. Y., Lv, J. Q., & Ji, K. W. (2017). Clinicopathological significance of SMAD4 loss in pancreatic ductal adenocarcinomas: a systematic review and meta-analysis. Oncotarget., 8(10), 16704.PubMedCrossRef
133.
Hao, J., Zhang, S., Zhou, Y., Liu, C., Hu, X., & Shao, C. (2011). MicroRNA 421 suppresses DPC4/Smad4 in pancreatic cancer. Biochemical and Biophysical Research Communications, 406(4), 552–557.PubMedCrossRef
134.
Wang, F., Xia, X., Yang, C., Shen, J., Mai, J., Kim, H. C., Kirui, D., Kang, Y. A., Fleming, J. B., Koay, E. J., & Mitra, S. (2018). SMAD4 gene mutation renders pancreatic cancer resistance to radiotherapy through promotion of autophagy. Clinical Cancer Research, 24(13), 3176–3185.PubMedPubMedCentralCrossRef
135.
Yamada, S., Fujii, T., Shimoyama, Y., Kanda, M., Nakayama, G., Sugimoto, H., Koike, M., Nomoto, S., Fujiwara, M., Nakao, A., & Kodera, Y. (2015). SMAD4 expression predicts local spread and treatment failure in resected pancreatic cancer. Pancreas., 44(4), 660–664.PubMedCrossRef
136.
Feig, C., Gopinathan, A., Neesse, A., Chan, D. S., Cook, N., & Tuveson, D. A. (2012). The pancreas cancer microenvironment. Clinical Cancer Research, 18(16), 4266–4276.PubMedPubMedCentralCrossRef
137.
Bapat, A. A., Hostetter, G., Von Hoff, D. D., & Han, H. (2011). Perineural inva-sion and associated pain in pancreatic cancer. Nature Reviews. Cancer, 11(10), 695–707.PubMedCrossRef
138.
139.
Feldmann, G., Beaty, R., Hruban, R. H., & Maitra, A. (2007). Molecular genetics of pancreatic intraepithelial neoplasia. J Hepatobiliary Pan-creat Surg, 14(3), 224–232.CrossRef
140.
Bryant, K. L., Mancias, J. D., Kimmelman, A. C., & Der, C. J. (2014). KRAS: feed-ing pancreatic cancer proliferation. Trends in Biochemical Sciences, 39(2), 91–100.PubMedPubMedCentralCrossRef
141.
Gaglio, D., Metallo, C. M., Gameiro, P. A., Hiller, K., Danna, L. S., Balestrieri, C., Alberghina, L., Stephanopoulos, G., & Chiaradonna, F. (2011). Oncogenic K-Ras decouples glucose and glutamine metabolism to support cancer cell growth. Molecular Systems Biology, 7, 523.PubMedPubMedCentralCrossRef
142.
Dell’ Antone, P. (2012). Energy metabolism in cancer cells: how to explain the Warburg and Crabtree effects? Medical Hypotheses, 79(3), 388–392.PubMedCrossRef
143.
Ying, H., Kimmelman, A. C., Lyssiotis, C. A., Hua, S., Chu, G. C., Fletcher-Sananikone, E., Locasale, J. W., Son, J., Zhang, H., Coloff, J. L., Yan, H., Wang, W., Chen, S., Viale, A., Zheng, H., Paik, J. H., Lim, C., Guimaraes, A. R., Martin, E. S., Chang, J., Hezel, A. F., Perry, S. R., Hu, J., Gan, B., Xiao, Y., Asara, J. M., Weissleder, R., Wang, Y. A., Chin, L., Cantley, L. C., et al. (2012). Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell, 149(3), 656–670.PubMedPubMedCentralCrossRef
144.
Ma, Z., Vocadlo, D. J., & Vosseller, K. (2013). Hyper-O-GlcNAcylation is anti-apoptotic and maintains constitutive NF-kappaB activity in pan-creatic cancer cells. The Journal of Biological Chemistry, 288(21), 15121–15130.PubMedPubMedCentralCrossRef
145.
Boros, L. G., Puigjaner, J., Cascante, M., Lee, W. N., Brandes, J. L., Bassilian, S., Yusuf, F. I., Williams, R. D., Muscarella, P., Melvin, W. S., & Schirmer, W. J. (1997). Oxythiamine and dehydroepiandrosterone inhibit the nonoxidative synthesis of ribose and tumor cell proliferation. Cancer Research, 57(19), 4242–4248.PubMed
146.
Butera, G., Pacchiana, R., Mullappilly, N., Margiotta, M., Bruno, S., Conti, P., Riganti, C., & Donadelli, M. (2018). Mutant p53 prevents GAPDH nuclear translocation in pancreatic cancer cells favoring glycolysis and 2-deoxyglucose sensitivity. Biochimica et Biophysica Acta, Molecular Cell Research, 1865(12), 1914–1923.PubMedCrossRef
147.
Schofield, H. K., Zeller, J., Espinoza, C., Halbrook, C. J., Del Vecchio, A., Magnuson, B., Fabo, T., Daylan, A. E. C., Kovalenko, I., Lee, H. J., Yan, W., Feng, Y., Karim, S. A., Kremer, D. M., Kumar-Sinha, C., Lyssiotis, C. A., Ljungman, M., Mor-ton, J. P., Galban, S., Fearon, E. R., & Pasca di Magliano, M. (2018). Mutant p53R270H drives altered metabolism and increased invasion in pan-creatic ductal adenocarcinoma. JCI Insight, 3(2), 97422.PubMedCrossRef
148.
Guillaumond, F., Leca, J., Olivares, O., Lavaut, M. N., Vidal, N., Berthezene, P., Dusetti, N. J., Loncle, C., Calvo, E., Turrini, O., Iovanna, J. L., Tomasini, R., & Vasseur, S. (2013). Strengthened glycolysis under hypoxia supports tumor symbiosis and hexosamine biosynthesis in pancreatic adeno-carcinoma. Proceedings of the National Academy of Sciences of the United States of America, 110(10), 3919–3924.PubMedPubMedCentralCrossRef
149.
Baek, G., Tse, Y. F., Hu, Z., Cox, D., Buboltz, N., McCue, P., Yeo, C. J., White, M. A., DeBerardinis, R. J., Knudsen, E. S., & Witkiewicz, A. K. (2014). MCT4 defines a glycolytic subtype of pancreatic cancer with poor prognosis and unique metabolic dependencies. Cell Reports, 9(6), 2233–2249.PubMedCrossRef
150.
Chaika, N. V., Gebregiworgis, T., Lewallen, M. E., Purohit, V., Radhakrish-nan, P., Liu, X., Zhang, B., Mehla, K., Brown, R. B., Caffrey, T., Yu, F., Johnson, K. R., Powers, R., Hollingsworth, M. A., & Singh, P. K. (2012). MUC1 mucin stabilizes and activates hypoxia-inducible factor 1 alpha to regulate metabolism in pancreatic cancer. Proceedings of the National Academy of Sciences of the United States of America, 109(34), 13787–13792.PubMedPubMedCentralCrossRef
151.
Shi, M., Cui, J., Du, J., Wei, D., Jia, Z., Zhang, J., Zhu, Z., Gao, Y., & Xie, K. (2014). A novel KLF4/LDHA signaling pathway regulates aerobic glycolysis in and progression of pancreatic cancer. Clinical Cancer Research, 20(16), 4370–4380.PubMedPubMedCentralCrossRef
152.
Swierczynski, J., Hebanowska, A., & Sledzinski, T. (2014). Role of abnor-mal lipid metabolism in development, progression, diagnosis and therapy of pancreatic cancer. World Journal of Gastroenterology, 20(9), 2279–2303.PubMedPubMedCentralCrossRef
153.
Hatzivassiliou, G., Zhao, F., Bauer, D. E., Andreadis, C., Shaw, A. N., Dhanak, D., Hingorani, S. R., Tuveson, D. A., & Thompson, C. B. (2005). ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell, 8(4), 311–321.PubMedCrossRef
154.
Takahashi, M., Hori, M., Ishigamori, R., Mutoh, M., Imai, T., & Nakagama, H. (2018). Fatty pancreas: a possible risk factor for pancreatic cancer in animals and humans. Cancer Science, 109(10), 3013–3023.PubMedPubMedCentralCrossRef
155.
Waddington, C. H. (1942). The epigenotype. Endeavour., 1, 18–20.
156.
157.
Berger, S. L., Kouzarides, T., Shiekhattar, R., & Shilatifard, A. (2009). An operational definition of epigenetics. Genes & Development, 23(7), 781–783.CrossRef
158.
Okano, M., Xie, S., & Li, E. (1998). Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nature Genetics, 19(3), 219–220.PubMedCrossRef
159.
Yen, R. W., Vertino, P. M., Nelkin, B. D., et al. (1992). Isolation and characterization of the cDNA encoding human DNA methyltransferase. Nucleic Acids Research, 20(9), 2287–2291.PubMedPubMedCentralCrossRef
160.
Li, A., Omura, N., Hong, S. M., & Goggins, M. (2010). Pancreatic cancer DNMT1 expression and sensitivity to DNMT1 inhibitors. Cancer Biology & Therapy, 9(4), 321–329.CrossRef
161.
Yoder, J. A., Walsh, C. P., & Bestor, T. H. (1997). Cytosine methylation and the ecology of intragenomic parasites. Trends in Genetics, 13(8), 335–340.PubMedCrossRef
162.
McCabe, M. T., Brandes, J. C., & Vertino, P. M. (2009). Cancer DNA methylation: molecular mechanisms and clinical implications. Clinical Cancer Research, 15(12), 3927–3937.PubMedPubMedCentralCrossRef
163.
Saxonov, S., Berg, P., & Brutlag, D. L. (2006). A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proceedings of the National Academy of Sciences, 103(5), 1412–1417.CrossRef
164.
Coulondre, C., Miller, J. H., Farabaugh, P. J., & Gilbert, W. (1978). Molecular basis of base substitution hotspots in Escherichia coli. Nature., 274(5673), 775.PubMedCrossRef
165.
Hendrich, B., Hardeland, U., Ng, H. H., Jiricny, J., & Bird, A. (2000). correction: The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites. Nature, 404(6777), 525.CrossRef
166.
Walsh, C. P., & Xu, G. L. Cytosine methylation and DNA repair. InDNA Methylation: Basic Mechanisms 2006 (pp. 283-315). Springer, Berlin. Heidelberg.
167.
Coetzee, G. A., Olumi, A. F., Spruck, C. H., & Jones, P. A. (1991). 5-Methylcytosine as an endogenous mutagen in the p53 tumor suppressor gene. InPrincess Takamatsu Symposia, 22, 207–219.
168.
Morgan, H. D., Santos, F., Green, K., Dean, W., & Reik, W. (2005). Epigenetic reprogramming in mammals. Human Molecular Genetics, 14(suppl_1), R47–R58.PubMedCrossRef
169.
170.
Ito, S., D’Alessio, A. C., Taranova, O. V., Hong, K., Sowers, L. C., & Zhang, Y. (2010). Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature., 466(7310), 1129.PubMedPubMedCentralCrossRef
171.
Li, J., Zhu, J., Hassan, M. M., Evans, D. B., Abbruzzese, J. L., & Li, D. (2007). K-ras mutation and p16 and preproenkephalin promoter hypermethylation in plasma DNA of pancreatic cancer patients: in relation to cigarette smoking. Pancreas., 34(1), 55.PubMedPubMedCentralCrossRef
172.
Tang, B., Li, Y., Qi, G., Yuan, S., Wang, Z., Yu, S., Li, B., & He, S. (2015). Clinicopathological significance of CDKN2A promoter hypermethylation frequency with pancreatic cancer. Scientific Reports, 5, 13563.PubMedPubMedCentralCrossRef
173.
Matsuoka, S., Edwards, M. C., Bai, C., et al. (1995). p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene. Genes & Development, 9(6), 650–662.CrossRef
174.
Sato, N., Matsubayashi, H., Abe, T., Fukushima, N., & Goggins, M. (2005). Epigenetic down-regulation of CDKN1C/p57KIP2 in pancreatic ductal neoplasms identified by gene expression profiling. Clinical Cancer Research, 11(13), 4681–4688.PubMedCrossRef
175.
176.
Meyyappan, M., Wong, H., Hull, C., & Riabowol, K. T. (1998). Increased expression of cyclin D2 during multiple states of growth arrest in primary and established cells. Molecular and Cellular Biology, 18(6), 3163–3172.PubMedPubMedCentralCrossRef
177.
Terris, B., Blaveri, E., Crnogorac-Jurcevic, T., Jones, M., Missiaglia, E., Ruszniewski, P., Sauvanet, A., & Lemoine, N. R. (2002). Characterization of gene expression profiles in intraductal papillary-mucinous tumors of the pancreas. The American Journal of Pathology., 160(5), 1745–1754.PubMedPubMedCentralCrossRef
178.
Matsubayashi, H., Sato, N., Fukushima, N., Yeo, C. J., Walter, K. M., Brune, K., Sahin, F., Hruban, R. H., & Goggins, M. (2003). Methylation of cyclin D2 is observed frequently in pancreatic cancer but is also an age-related phenomenon in gastrointestinal tissues. Clinical Cancer Research, 9(4), 1446–1452.PubMed
179.
Li, J., Zhu, J., Hassan, M. M., Evans, D. B., Abbruzzese, J. L., & Li, D. (2007). K-ras mutation and p16 and preproenkephalin promoter hypermethylation in plasma DNA of pancreatic cancer patients: in relation to cigarette smoking. Pancreas., 34(1), 55.PubMedPubMedCentralCrossRef
180.
Zagon, I. S., Roesener, C. D., Verderame, M. F., Ohlsson-Wilhelm, B. M., Levin, R. J., & McLaughlin, P. J. (2000). Opioid growth factor regulates the cell cycle of human neoplasias. International Journal of Oncology, 17(5), 1053–1114.PubMed
181.
Comb, M., & Goodman, H. M. (1990). CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2. Nucleic Acids Research, 18(13), 3975–3982.PubMedPubMedCentralCrossRef
182.
Fukushima, N., Sato, N., Ueki, T., Rosty, C., Walter, K. M., Wilentz, R. E., Yeo, C. J., Hruban, R. H., & Goggins, M. (2002). Aberrant methylation of preproenkephalin and p16 genes in pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma. The American Journal of Pathology., 160(5), 1573–1581.PubMedPubMedCentralCrossRef
183.
Wen, Z., Zhong, Z., & Darnell Jr., J. E. (1995). Maximal activation of transcription by Statl and Stat3 requires both tyrosine and serine phosphorylation. Cell., 82(2), 241–250.PubMedCrossRef
184.
Naka, T., Narazaki, M., Hirata, M., Matsumoto, T., Minamoto, S., Aono, A., Nishimoto, N., Kajita, T., Taga, T., Yoshizaki, K., & Akira, S. (1997). Structure and function of a new STAT-induced STAT inhibitor. Nature., 387(6636), 924.PubMedCrossRef
185.
Komazaki, T., Nagai, H., Emi, M., Terada, Y., Yabe, A., Jin, E., Kawanami, O., Konishi, N., Moriyama, Y., Naka, T., & Kishimoto, T. (2004). Hypermethylation-associated inactivation of the SOCS-1 gene, a JAK/STAT inhibitor, in human pancreatic cancers. Japanese Journal of Clinical Oncology, 34(4), 191–194.PubMedCrossRef
186.
Mah, K. M., & Weiner, J. A. (2017). Regulation of Wnt signaling by protocadherins. InSeminars in Cell & Developmental Biology, 69, 158–171 Academic Press.
187.
Vincent, A., Omura, N., Hong, S. M., Jaffe, A., Eshleman, J., & Goggins, M. (2011). Genome-wide analysis of promoter methylation associated with gene expression profile in pancreatic adenocarcinoma. Clinical Cancer Research, 17(13), 4341–4354.PubMedPubMedCentralCrossRef
188.
Curia, M. C., Fantini, F., Lattanzio, R., Tavano, F., Di Mola, F., Piantelli, M., Battista, P., Di Sebastiano, P., & Cama, A. (2019). High methylation levels of PCDH10 predict poor prognosis in patients with pancreatic ductal adenocarcinoma. BMC Cancer, 19(1), 452.PubMedPubMedCentralCrossRef
189.
Christoffels, V. M., Keijser, A. G., Houweling, A. C., Clout, D. E., & Moorman, A. F. (2000). Patterning the embryonic heart: identification of five mouse Iroquois homeobox genes in the developing heart. Developmental Biology, 224(2), 263–274.PubMedCrossRef
190.
Chakma, K., Gu, Z., Motoi, F., Unno, M., Horii, A., & Fukushige, S. (2019). DNA hypermethylation of IRX4 is a frequent event that may confer growth advantage to pancreatic cancer cells., 01, 821–821.
191.
Eissa, M. A., Lerner, L., Abdelfatah, E., Shankar, N., Canner, J. K., Hasan, N. M., Yaghoobi, V., Huang, B., Kerner, Z., Takaesu, F., & Wolfgang, C. (2019). Promoter methylation of ADAMTS1 and BNC1 as potential biomarkers for early detection of pancreatic cancer in blood. Clinical Epigenetics, 11(1), 59.PubMedPubMedCentralCrossRef
192.
Sato, N., Fukushima, N., Matsubayashi, H., Iacobuzio-Donahue, C. A., Yeo, C. J., & Goggins, M. (2006). Aberrant methylation of Reprimo correlates with genetic instability and predicts poor prognosis in pancreatic ductal adenocarcinoma. Cancer., 107(2), 251–257.PubMedCrossRef
193.
Ueki, T., Toyota, M., Sohn, T., Yeo, C. J., Issa, J. P., Hruban, R. H., & Goggins, M. (2000). Hypermethylation of multiple genes in pancreatic adenocarcinoma. Cancer Research, 60(7), 1835–1839.PubMed
194.
Sato, N., Fukushima, N., Maitra, A., Matsubayashi, H., Yeo, C. J., Cameron, J. L., Hruban, R. H., & Goggins, M. (2003). Discovery of novel targets for aberrant methylation in pancreatic carcinoma using high-throughput microarrays. Cancer Research, 63(13), 3735–3742.PubMed
195.
Li, A., Omura, N., Hong, S. M., Vincent, A., Walter, K., Griffith, M., Borges, M., & Goggins, M. (2010). Pancreatic cancers epigenetically silence SIP1 and hypomethylate and overexpress miR-200a/200b in association with elevated circulating miR-200a and miR-200b levels. Cancer Research, 70(13), 5226–5237.PubMedPubMedCentralCrossRef
196.
Sato, N., Fukushima, N., Maehara, N., Matsubayashi, H., Koopmann, J., Su, G. H., Hruban, R. H., & Goggins, M. (2003). SPARC/osteonectin is a frequent target for aberrant methylation in pancreatic adenocarcinoma and a mediator of tumor–stromal interactions. Oncogene., 22(32), 5021.PubMedCrossRef
197.
Omura, N., Li, C. P., Li, A., Hong, S. M., Walter, K., Jimeno, A., Hidalgo, M., & Goggins, M. (2008). Genome-wide profiling at methylated promoters in pancreatic adenocarcinoma. Cancer Biology & Therapy, 7(7), 1146–1156.CrossRef
198.
Li, J., Wu, H., Li, W., Yin, L., Guo, S., Xu, X., Ouyang, Y., Zhao, Z., Liu, S., Tian, Y., & Tian, Z. (2016). Downregulated miR-506 expression facilitates pancreatic cancer progression and chemoresistance via SPHK1/Akt/NF-κB signaling. Oncogene., 35(42), 5501.PubMedPubMedCentralCrossRef
199.
Vincent, A., Omura, N., Hong, S. M., Jaffe, A., Eshleman, J., & Goggins, M. (2011). Genome-wide analysis of promoter methylation associated with gene expression profile in pancreatic adenocarcinoma. Clinical Cancer Research, 17(13), 4341–4354.PubMedPubMedCentralCrossRef
200.
Thompson, M. J., Rubbi, L., Dawson, D. W., Donahue, T. R., & Pellegrini, M. (2015). Pancreatic cancer patient survival correlates with DNA methylation of pancreas development genes. PLoS One, 10(6), e0128814.PubMedPubMedCentralCrossRef
201.
Gama-Sosa, M. A., Slagel, V. A., Trewyn, R. W., et al. (1983). The 5- methylcytosine content of DNA from human tumors. Nucleic Acids Research, 11, 6883–6894.PubMedPubMedCentralCrossRef
202.
Feinberg, A. P., Vogelstein, B., et al. (1983). Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature., 301, 89–92.PubMedCrossRef
203.
Rauch, T. A., Zhong, X., Wu, X., et al. (2008). High-resolution mapping of DNA hypermethylation and hypomethylation in lung cancer. Proceedings of the National Academy of Sciences of the United States of America, 105, 252–257.PubMedCrossRef
204.
Ehrlich, M. (2002). DNA methylation in cancer: too much, but also too little. Oncogene., 21, 5400–5413.PubMedCrossRef
205.
Ohike, N., Maass, N., Mundhenke, C., et al. (2003). Clinicopathological significance and molecular regulation of maspin expression in ductal adenocarcinoma of the pancreas. Cancer Letters, 199(2), 193–200.PubMedCrossRef
206.
Sato, N., Maitra, A., Fukushima, N., et al. (2003). Frequent hypomethylation of multiple genes overexpressed in pancreatic ductal adenocarcinoma. Cancer Research, 63(14), 4158–4166.PubMed
207.
Chen, H., Kong, Y., Yao, Q., Zhang, X., Fu, Y., Li, J., Liu, C., & Wang, Z. (2019). Three hypomethylated genes were associated with poor overall survival in pancreatic cancer patients. Aging (Albany NY), 11(3), 885.CrossRef
208.
Zhu, Y., Zhang, J. J., Zhu, R., Zhu, Y., Liang, W. B., Gao, W. T., Yu, J. B., Xu, Z. K., & Miao, Y. (2011). The increase in the expression and hypomethylation of MUC4 gene with the progression of pancreatic ductal adenocarcinoma. Medical Oncology, 28(1), 175–184.CrossRef
209.
Sekine, H., Chen, N., Sato, K., Saiki, Y., Yoshino, Y., Umetsu, Y., Jin, G., Nagase, H., Gu, Z., Fukushige, S., & Sunamura, M. (2012). S100A4, frequently overexpressed in various human cancers, accelerates cell motility in pancreatic cancer cells. Biochemical and Biophysical Research Communications, 429(3-4), 214–219.PubMedCrossRef
210.
Feinberg, A. P., Koldobskiy, M. A., & Göndör, A. (2016). Epigenetic modulators, modifiers and mediators in cancer aetiology and progression. Nature Reviews. Genetics, 17(5), 284.PubMedPubMedCentralCrossRef
211.
Abukiwan A, Berger MR. Epigenetics: dissecting gene expression alteration in PDAC. In Advances in DNA Repair 2018 Nov 5. IntechOpen.
212.
Ramassone, A., Pagotto, S., Veronese, A., & Visone, R. (2018). Epigenetics and microRNAs in cancer. International Journal of Molecular Sciences, 19(2), 459.PubMedCentralCrossRef
213.
Iguchi, E., Safgren, S. L., Marks, D. L., Olson, R. L., & Fernandez-Zapico, M. E. (2016). Focus: epigenetics: pancreatic cancer, a mis-interpreter of the epigenetic language. The Yale Journal of Biology and Medicine., 89(4), 575.PubMedPubMedCentral
214.
Fernandez, A. F., Assenov, Y., Martin-Subero, J. I., Balint, B., Siebert, R., Taniguchi, H., Yamamoto, H., Hidalgo, M., Tan, A. C., Galm, O., et al. (2012). A DNA methylation fingerprint of 1628 human samples. Genome Research, 22(2), 407–419.PubMedPubMedCentralCrossRef
215.
Hao, X., Luo, H., Krawczyk, M., Wei, W., Wang, W., Wang, J., Flagg, K., Hou, J., Zhang, H., Yi, S., et al. (2017). DNA methylation markers for diagnosis and prognosis of common cancers. Proceedings of the National Academy of Sciences of the United States of America, 114(28), 7414–7419.PubMedPubMedCentralCrossRef
216.
Rodríguez-Rodero, S., Fernández, A. F., Fernández-Morera, J. L., Castro-Santos, P., Bayon, G. F., Ferrero, C., Urdinguio, R. G., Gonzalez-Marquez, R., Suarez, C., Fernández-Vega, I., & Fresno Forcelledo, M. F. (2013). DNA methylation signatures identify biologically distinct thyroid cancer subtypes. The Journal of Clinical Endocrinology & Metabolism., 98(7), 2811–2821.CrossRef
217.
Baylin, S. B., & Jones, P. A. (2011). A decade of exploring the cancer epigenome – biological and translational implications. Nature Reviews. Cancer, 11(10), 726–734.PubMedPubMedCentralCrossRef
218.
Moran, S., Martinez-Cardus, A., Sayols, S., Musulen, E., Balana, C., Estival-Gonzalez, A., Moutinho, C., Heyn, H., Diaz-Lagares, A., de Moura, M. C., et al. (2016). Epigenetic profiling to classify cancer of unknown primary: a multicentre, retrospective analysis. The Lancet Oncology, 17(10), 1386–1395.PubMedCrossRef
219.
Kanwal, R., & Gupta, S. (2012). Epigenetic modifications in cancer. Clinical Genetics, 81(4), 303–311.PubMedCrossRef
220.
Hosseini A, Minucci S (2018). Alterations of histone modifications in cancer. In: Epigenetics in human disease, vol. 6. 2nd ed; p. 141–217.
221.
Baylin, S. B., & Jones, P. A. (2016). Epigenetic determinants of cancer. Cold Spring Harbor Perspectives in Biology, 8, 9.CrossRef
222.
Berdasco, M., & Esteller, M. (2018). Clinical epigenetics: seizing opportunities for translation. Nature Reviews. Genetics.
223.
Rodriguez-Paredes, M., & Esteller, M. (2011). Cancer epigenetics reaches mainstream oncology. Nature Medicine, 17(3), 330–339.PubMedCrossRef
224.
Allis, C. D., & Jenuwein, T. (2016). The molecular hallmarks of epigenetic control. Nature Reviews. Genetics, 17(8), 487–500.PubMedCrossRef
225.
Herman, J. G., & Baylin, S. B. (2003). Gene silencing in cancer in association with promoter hypermethylation. The New England Journal of Medicine, 349(21), 2042–2054.PubMedCrossRef
226.
Palii, S. S., Van Emburgh, B. O., Sankpal, U. T., Brown, K. D., & Robertson, K. D. (2008). DNA methylation inhibitor 5-Aza-2′-deoxycytidine induces reversible genomewide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B. Molecular and Cellular Biology, 28(2), 752–771.PubMedCrossRef
227.
Chiappinelli, K. B., Strissel, P. L., Desrichard, A., Li, H., Henke, C., Akman, B., Hein, A., Rote, N. S., Cope, L. M., Snyder, A., et al. (2015). Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell., 162(5), 974–986.PubMedPubMedCentralCrossRef
228.
Roulois, D., Loo Yau, H., Singhania, R., Wang, Y., Danesh, A., Shen, S. Y., Han, H., Liang, G., Jones, P. A., Pugh, T. J., et al. (2015). DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell., 162(5), 961–973.PubMedPubMedCentralCrossRef
229.
Xue, K., Gu, J. J., Zhang, Q., Mavis, C., Hernandez-Ilizaliturri, F. J., Czuczman, M. S., & Guo, Y. (2016). Vorinostat, a histone deacetylase (HDAC) inhibitor, promotes cell cycle arrest and re-sensitizes rituximab- and chemo-resistant lymphoma cells to chemotherapy agents. Journal of Cancer Research and Clinical Oncology, 142(2), 379–387.PubMedCrossRef
230.
Kronfol, M. M., Dozmorov, M. G., Huang, R., Slattum, P. W., & McClay, J. L. (2017). The role of epigenomics in personalized medicine. Expert Rev Precis Med Drug Dev., 2(1), 33–45.PubMedPubMedCentralCrossRef
231.
Cameron, E. E., Bachman, K. E., Myohanen, S., Herman, J. G., & Baylin, S. B. (1999). Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nature Genetics, 21(1), 103–107.PubMedCrossRef
232.
Juergens, R. A., Wrangle, J., Vendetti, F. P., Murphy, S. C., Zhao, M., Coleman, B., Sebree, R., Rodgers, K., Hooker, C. M., Franco, N., et al. (2011). Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer. Cancer Discovery, 1(7), 598–607.PubMedPubMedCentralCrossRef
233.
Jones, P. A., Issa, J. P., & Baylin, S. (2016). Targeting the cancer epigenome for therapy. Nature Reviews. Genetics, 17(10), 630–641.PubMedCrossRef
234.
Ezzati, M., Henley, S. J., Lopez, A. D., & Thun, M. J. (2005). Role of smoking in global and regional cancer epidemiology: current patterns and data needs. International Journal of Cancer, 116(6), 963–971.PubMedCrossRef
235.
Jarosz, M., Sekuła, W., & Rychlik, E. (2012). Influence of diet and tobacco smoking on pancreatic cancer incidence in Poland in 1960–2008. Gastroenterology Research and Practice, 2012.
236.
Wang, Y. T., Gou, Y. W., Jin, W. W., Xiao, M., & Fang, H. Y. (2016). Association between alcohol intake and the risk of pancreatic cancer: a dose–response meta-analysis of cohort studies. BMC Cancer, 16(1), 212.PubMedPubMedCentralCrossRef
237.
Jacobs, E. J., Chanock, S. J., Fuchs, C. S., LaCroix, A., McWilliams, R. R., Steplowski, E., Stolzenberg-Solomon, R. Z., Arslan, A. A., Bueno-de-Mesquita, H. B., Gross, M., & Helzlsouer, K. (2010). Family history of cancer and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan). International Journal of Cancer, 127(6), 1421–1428.PubMedPubMedCentralCrossRef
238.
Davoodi, S. H., Malek-Shahabi, T., Malekshahi-Moghadam, A., Shahbazi, R., & Esmaeili, S. (2013). Obesity as an important risk factor for certain types of cancer. Iranian Journal of Cancer Prevention., 6(4), 186.PubMedPubMedCentral
239.
Aune, D., Greenwood, D. C., Chan, D. S., Vieira, R., Vieira, A. R., Navarro Rosenblatt, D. A., Cade, J. E., Burley, V. J., & Norat, T. (2011). Body mass index, abdominal fatness and pancreatic cancer risk: a systematic review and non-linear dose–response meta-analysis of prospective studies. Annals of Oncology, 23(4), 843–852.PubMedCrossRef
240.
Rawla, P., Sunkara, T., & Gaduputi, V. (2019). Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World Journal of Oncology., 10(1), 10.PubMedPubMedCentralCrossRef
241.
Metadaten
Titel
An overview of genetic mutations and epigenetic signatures in the course of pancreatic cancer progression
verfasst von
Aamir Ali Khan
Xinhui Liu
Xinlong Yan
Muhammad Tahir
Sakhawat Ali
Hua Huang
Publikationsdatum
10.01.2021
Verlag
Springer US
Erschienen in
Cancer and Metastasis Reviews / Ausgabe 1/2021
Print ISSN: 0167-7659
Elektronische ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-020-09952-0

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