nach oben

Digestive Diseases and Sciences

Erschienen in:

01.03.2015 | Review

The Molecular Pathogenesis of Colorectal Cancer and Its Potential Application to Colorectal Cancer Screening

verfasst von: William M. Grady, Sanford D. Markowitz

Erschienen in: Digestive Diseases and Sciences | Ausgabe 3/2015

Einloggen, um Zugang zu erhalten

Abstract

Introduction

Advances in our understanding of the molecular genetics and epigenetics of colorectal cancer have led to novel insights into the pathogenesis of this common cancer. These advances have revealed that there are molecular subtypes of colon polyps and colon cancer and that these molecular subclasses have unique and discrete clinical and pathological features. Although the molecular characterization of these subgroups of colorectal polyps and cancer is only partially understood at this time, it does appear likely that classifying colon polyps and cancers based on their genomic instability and/or epigenomic instability status will eventually be useful for informing approaches for the prevention and early detection of colon polyps and colorectal cancer.

Conclusions

In this review, we will discuss our current understanding of the molecular pathogenesis of the polyp to cancer sequence and the potential to use this information to direct screening and prevention programs.

Vogelstein B, Fearon E, Hamilton S, et al. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988;319:525–532.PubMed

Goldstein NS. Serrated pathway and APC (conventional)-type colorectal polyps: molecular-morphologic correlations, genetic pathways, and implications for classification. Am J Clin Pathol. 2006;125:146–153.PubMed

Jass JR. Hyperplastic polyps and colorectal cancer: is there a link? Clin Gastroenterol Hepatol. 2004;2:1–8.PubMed

Bettington M, Walker N, Clouston A, et al. The serrated pathway to colorectal carcinoma: current concepts and challenges. Histopathology. 2013;62:367–386.PubMed

Baker K, Zhang Y, Jin C, et al. Proximal versus distal hyperplastic polyps of the colorectum: different lesions or a biological spectrum? J Clin Pathol. 2004;57:1089–1093.PubMedCentralPubMed

Burnett-Hartman AN, Newcomb PA, Potter JD, et al. Genomic aberrations occurring in subsets of serrated colorectal lesions but not conventional adenomas. Cancer Res. 2013;73:2863–2872.PubMed

Noffsinger AE. Serrated polyps and colorectal cancer: new pathway to malignancy. Annu Rev Pathol. 2009;4:343–364.PubMed

Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.PubMed

Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–674.PubMed

10.

Little MP, Vineis P, Li G. A stochastic carcinogenesis model incorporating multiple types of genomic instability fitted to colon cancer data. J Theor Biol. 2008;254:229–238.PubMed

11.

Grady WM, Carethers JM. Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology. 2008;135:1079–1099.PubMedCentralPubMed

12.

Brennan CW, Verhaak RG, McKenna A, et al. The somatic genomic landscape of glioblastoma. Cell. 2013;155:462–477.PubMedCentralPubMed

13.

Walther A, Johnstone E, Swanton C, et al. Genetic prognostic and predictive markers in colorectal cancer. Nat Rev Cancer. 2009;9:489–499.PubMed

14.

Walther A, Houlston R, Tomlinson I. Association between chromosomal instability and prognosis in colorectal cancer: a meta-analysis. Gut. 2008;57:941–950.PubMed

15.

Wang WL, Huang HC, Kao SH, et al. Slug is temporally regulated by cyclin E in cell cycle and controls genome stability. Oncogene. 2014. doi:10.1038/onc.2014.58.

16.

Geigl JB, Obenauf AC, Schwarzbraun T, et al. Defining ‘chromosomal instability’. Trends Genet. 2008;24:64–69.PubMed

17.

Shin HJ, Baek KH, Jeon AH, et al. Dual roles of human BubR1, a mitotic checkpoint kinase, in the monitoring of chromosomal instability. Cancer Cell. 2003;4:483–497.PubMed

18.

Anderhub SJ, Kramer A, Maier B. Centrosome amplification in tumorigenesis. Cancer Lett. 2012;322:8–17.PubMed

19.

Roger L, Jones RE, Heppel NH, et al. Extensive telomere erosion in the initiation of colorectal adenomas and its association with chromosomal instability. J Natl Cancer Inst. 2013;105:1202–1211.PubMed

20.

Gilad O, Nabet BY, Ragland RL, et al. Combining ATR suppression with oncogenic Ras synergistically increases genomic instability, causing synthetic lethality or tumorigenesis in a dosage-dependent manner. Cancer Res. 2010;70:9693–9702.PubMedCentralPubMed

21.

Maley CC, Galipeau PC, Finley JC, et al. Genetic clonal diversity predicts progression to esophageal adenocarcinoma. Nat Genet. 2006;38:468–473.PubMed

22.

Hermsen M, Postma C, Baak J, et al. Colorectal adenoma to carcinoma progression follows multiple pathways of chromosomal instability. Gastroenterology. 2002;123:1109–1119.PubMed

23.

Grady WM. Genomic instability and colon cancer. Cancer Metastas Rev. 2004;23:11–27.

24.

Boland C, Thibodeau S, Hamilton S, et al. A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determinate of microsatellite instability in colorectal cancer. Cancer Res. 1998;58:5248–5257.PubMed

25.

Bacher JW, Flanagan LA, Smalley RL, et al. Development of a fluorescent multiplex assay for detection of MSI-high tumors. Dis Markers. 2004;20:237–250.PubMedCentralPubMed

26.

Baron JA, Cole BF, Sandler RS, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med. 2003;348:891–899.PubMed

27.

Popat S, Hubner R, Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol. 2005;23:609–618.PubMed

28.

Fallik D, Borrini F, Boige V, et al. Microsatellite instability is a predictive factor of the tumor response to irinotecan in patients with advanced colorectal cancer. Cancer Res. 2003;63:5738–5744.PubMed

29.

Jo WS, Carethers JM. Chemotherapeutic implications in microsatellite unstable colorectal cancer. Cancer Biomark. 2006;2:51–60.PubMed

30.

Sargent D, Marsoni S, Thibodeau SN, et al. Confirmation of deficient mismatch repair (dMMR) as a predictive marker for lack of benefit from 5-FU based chemotherapy in stage II and III colon cancer (CC): a pooled molecular reanalysis of randomized chemotherapy trials. J Clin Oncol. 2008;26:Abstr. 4008.

31.

O’Brien MJ, Yang S, Mack C, et al. Comparison of microsatellite instability, CpG island methylation phenotype, BRAF and KRAS status in serrated polyps and traditional adenomas indicates separate pathways to distinct colorectal carcinoma end points. Am J Surg Pathol. 2006;30:1491–1501.PubMed

32.

Inoue A, Okamoto K, Fujino Y, et al. B-RAF mutation and accumulated gene methylation in aberrant crypt foci (ACF), sessile serrated adenoma/polyp (SSA/P) and cancer in SSA/P. Br J Cancer. 2014. doi:10.1038/bjc.2014.545.

33.

Toiyama Y, Hur K, Tanaka K, et al. Serum miR-200c is a novel prognostic and metastasis-predictive biomarker in patients with colorectal cancer. Ann Surg. 2014;259:735–743.PubMed

34.

Calabrese P, Tsao JL, Yatabe Y, et al. Colorectal pretumor progression before and after loss of DNA mismatch repair. Am J Pathol. 2004;164:1447–1453.PubMedCentralPubMed

35.

Ricciardone MD, Ozcelik T, Cevher B, et al. Human MLH1 deficiency predisposes to hematological malignancy and neurofibromatosis type 1. Cancer Res. 1999;59:290–293.PubMed

36.

Kane M, Loda M, Gaida G, et al. Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res. 1997;57:808–811.PubMed

37.

Domingo E, Laiho P, Ollikainen M, et al. BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing. J Med Genet. 2004;41:664–668.PubMedCentralPubMed

38.

Wang L, Cunningham JM, Winters JL, et al. BRAF mutations in colon cancer are not likely attributable to defective DNA mismatch repair. Cancer Res. 2003;63:5209–5212.PubMed

39.

Suzuki H, Igarashi S, Nojima M, et al. IGFBP7 is a p53-responsive gene specifically silenced in colorectal cancer with CpG island methylator phenotype. Carcinogenesis. 2010;31:342–349.PubMed

40.

Toyota M, Ahuja N, Ohe-Toyota M, et al. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci USA. 1999;96:8681–8686.PubMedCentralPubMed

41.

Issa JP, Shen L, Toyota M. CIMP, at last. Gastroenterology. 2005;129:1121–1124.PubMed

42.

Issa JP. Aging and epigenetic drift: a vicious cycle. J Clin Invest. 2014;124:24–29.PubMedCentralPubMed

43.

Tahara T, Yamamoto E, Madireddi P, et al. Colorectal carcinomas with CpG island methylator phenotype 1 frequently contain mutations in chromatin regulators. Gastroenterology. 2014;146:530–538 e5.PubMedCentralPubMed

44.

Bachman KE, Park BH, Rhee I, et al. Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene. Cancer Cell. 2003;3:89–95.PubMed

45.

Hinshelwood RA, Melki JR, Huschtscha LI, et al. Aberrant de novo methylation of the p16INK4A CpG island is initiated post gene silencing in association with chromatin remodelling and mimics nucleosome positioning. Hum Mol Genet. 2009;18:3098–3109.PubMed

46.

Limsui D, Vierkant RA, Tillmans LS, et al. Cigarette smoking and colorectal cancer risk by molecularly defined subtypes. J Natl Cancer Inst. 2010;102:1012–1022.PubMedCentralPubMed

47.

Ichimura K. Molecular pathogenesis of IDH mutations in gliomas. Brain Tumor Pathol. 2012;29:131–139.PubMed

48.

The Cancer Genome Atlas Research Network*. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455:1061–1068.

49.

Bredel M, Scholtens DM, Harsh GR, et al. A network model of a cooperative genetic landscape in brain tumors. JAMA. 2009;302:261–275.PubMed

50.

Hinoue T, Weisenberger DJ, Pan F, et al. Analysis of the association between CIMP and BRAF in colorectal cancer by DNA methylation profiling. PLoS One. 2009;4:e8357.PubMedCentralPubMed

51.

Nosho K, Irahara N, Shima K, et al. Comprehensive biostatistical analysis of CpG island methylator phenotype in colorectal cancer using a large population-based sample. PLoS One. 2008;3:e3698.PubMedCentralPubMed

52.

Weisenberger DJ, Siegmund KD, Campan M, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 2006;38:787–793.PubMed

53.

Barault L, Charon-Barra C, Jooste V, et al. Hypermethylator phenotype in sporadic colon cancer: study on a population-based series of 582 cases. Cancer Res. 2008;68:8541–8546.PubMed

54.

Shen L, Toyota M, Kondo Y, et al. Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer. Proc Natl Acad Sci USA. 2007;104:18654–18659.PubMedCentralPubMed

55.

Shiovitz S, Bertagnolli MM, Renfro LA, et al. CpG island methylator phenotype is associated with response to adjuvant irinotecan-based therapy for stage 3 colon cancer. Gastroenterology. 2014;111(3):598–602.

56.

Iacopetta B, Kawakami K, Watanabe T. Predicting clinical outcome of 5-fluorouracil-based chemotherapy for colon cancer patients: is the CpG island methylator phenotype the 5-fluorouracil-responsive subgroup? Int J Clin Oncol. 2008;13:498–503.PubMed

57.

Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med. 2014;370:1287–1297.PubMed

58.

Chen WD, Han ZJ, Skoletsky J, et al. Detection in fecal DNA of colon cancer-specific methylation of the nonexpressed vimentin gene. J Natl Cancer Inst. 2005;97:1124–1132.PubMed

59.

Itzkowitz S, Brand R, Jandorf L, et al. A simplified, noninvasive stool DNA test for colorectal cancer detection. Am J Gastroenterol. 2008;103:2862–2870.PubMed

60.

Matsuzaki K, Deng G, Tanaka H, et al. The relationship between global methylation level, loss of heterozygosity, and microsatellite instability in sporadic colorectal cancer. Clin Cancer Res. 2005;11:8564–8569.PubMed

61.

Rodriguez J, Frigola J, Vendrell E, et al. Chromosomal instability correlates with genome-wide DNA demethylation in human primary colorectal cancers. Cancer Res. 2006;66:8462–9468.PubMed

62.

Hur K, Cejas P, Feliu J, et al. Hypomethylation of long interspersed nuclear element-1 (LINE-1) leads to activation of proto-oncogenes in human colorectal cancer metastasis. Gut. 2014;63(4):635–646.

63.

Karpf AR, Matsui S. Genetic disruption of cytosine DNA methyltransferase enzymes induces chromosomal instability in human cancer cells. Cancer Res. 2005;65:8635–8639.PubMed

64.

Doege CA, Inoue K, Yamashita T, et al. Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2. Nature. 2012;488:652–655.PubMed

65.

Dulak AM, Stojanov P, Peng S, et al. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat Genet. 2013;45:478–486.PubMed

66.

Ogino S, Kawasaki T, Nosho K, et al. LINE-1 hypomethylation is inversely associated with microsatellite instability and CpG island methylator phenotype in colorectal cancer. Int J Cancer. 2008;122:2767–2773.PubMedCentralPubMed

67.

Pino MS, Chung DC. The chromosomal instability pathway in colon cancer. Gastroenterology. 2010;138:2059–2072.PubMedCentralPubMed

68.

Aaltonen LA, Peltomaki P, Mecklin JP, et al. Replication errors in benign and malignant tumors from hereditary nonpolyposis colorectal cancer patients. Cancer Res. 1994;54:1645–1648.PubMed

69.

Jacoby R, Marshall D, Kailas S, et al. Genetic instability associated with adenoma to carcinoma progression in hereditary nonpolyposis colon cancer. Gastroenterology. 1995;109:73–82.PubMed

70.

Bomme L, Bardi G, Pandis N, et al. Cytogenetic analysis of colorectal adenomas: karyotypic comparisons of synchronous tumors. Cancer Genet Cytogenet. 1998;106:66–71.PubMed

71.

Ried T, Heselmeyer-Haddad K, Blegen H, et al. Genomic changes defining the genesis, progression, and malignancy potential in solid human tumors: a phenotype/genotype correlation. Genes Chromosom Cancer. 1999;25:195–204.PubMed

72.

Stoler DL, Chen N, Basik M, et al. The onset and extent of genomic instability in sporadic colorectal tumor progression. Proc Natl Acad Sci USA. 1999;96:15121–15126.PubMedCentralPubMed

73.

Meijer GA, Hermsen MA, Baak JP, et al. Progression from colorectal adenoma to carcinoma is associated with non- random chromosomal gains as detected by comparative genomic hybridisation. J Clin Pathol. 1998;51:901–909.PubMedCentralPubMed

74.

Jones AM, Thirlwell C, Howarth KM, et al. Analysis of copy number changes suggests chromosomal instability in a minority of large colorectal adenomas. J Pathol. 2007;213:249–256.PubMed

75.

Shih IM, Zhou W, Goodman SN, et al. Evidence that genetic instability occurs at an early stage of colorectal tumorigenesis. Cancer Res. 2001;61:818–822.PubMed

76.

Neuville A, Nicolet C, Meyer N, et al. Histologic characteristics of non-microsatellite-instable colon adenomas correlate with distinct molecular patterns. Hum Pathol. 2011;42:244–253.PubMed

77.

Leslie A, Stewart A, Baty DU, et al. Chromosomal changes in colorectal adenomas: relationship to gene mutations and potential for clinical utility. Genes Chromosom Cancer. 2006;45:126–135.PubMed

78.

Nowak MA, Komarova NL, Sengupta A, et al. The role of chromosomal instability in tumor initiation. Proc Natl Acad Sci USA. 2002;21:21.

79.

Lengauer C, Kinzler KW, Vogelstein B. Genetic instability in colorectal cancers. Nature. 1997;386:623–627.PubMed

80.

Fodde R, Kuipers J, Rosenberg C, et al. Mutations in the APC tumour suppressor gene cause chromosomal instability. Nat Cell Biol. 2001;3:433–438.PubMed

81.

Kaplan KB, Burds AA, Swedlow JR, et al. A role for the adenomatous polyposis coli protein in chromosome segregation. Nat Cell Biol. 2001;3:429–432.PubMed

82.

Spirio LN, Samowitz W, Robertson J, et al. Alleles of APC modulate the frequency and classes of mutations that lead to colon polyps. Nat Genet. 1998;20:385–388.PubMed

83.

Kim KM, Lee EJ, Ha S, et al. Molecular features of colorectal hyperplastic polyps and sessile serrated adenoma/polyps from Korea. Am J Surg Pathol. 2011;35:1274–1286.PubMed

84.

Beggs AD, Domingo E, Abulafi M, et al. A study of genomic instability in early preneoplastic colonic lesions. Oncogene. 2013;32:5333–5337.PubMedCentralPubMed

85.

Winawer S, Fletcher R, Rex D, et al. Colorectal cancer screening and surveillance: clinical guidelines and rationale—update based on new evidence. Gastroenterology. 2003;124:544–560.PubMed

86.

Pedroni M, Tamassia MG, Percesepe A, et al. Microsatellite instability in multiple colorectal tumors. Int J Cancer. 1999;81:1–5.PubMed

87.

Zauber P, Huang J, Sabbath-Solitare M, et al. Similarities of molecular genetic changes in synchronous and metachronous colorectal cancers are limited and related to the cancers’ proximities to each other. J Mol Diagn. 2013;15:652–660.PubMed

88.

Lawes DA, Pearson T, Sengupta S, et al. Is MSI-H of value in predicting the development of metachronous colorectal cancer? Eur J Cancer. 2006;42:473–476.PubMed

89.

Balleste B, Bessa X, Pinol V, et al. Detection of metachronous neoplasms in colorectal cancer patients: identification of risk factors. Dis Colon Rectum. 2007;50:971–980.PubMed

90.

Lam AK, Chan SS, Leung M. Synchronous colorectal cancer: clinical, pathological and molecular implications. World J Gastroenterol. 2014;20:6815–6820.PubMedCentralPubMed

91.

Chan AO, Broaddus RR, Houlihan PS, et al. CpG island methylation in aberrant crypt foci of the colorectum. Am J Pathol. 2002;160:1823–1830.PubMedCentralPubMed

92.

Luo L, Chen W, Pretlow T. CpG island methylation in aberrant crypt foci and cancers from the same patients. Int J Cancer. 2005;115:747–751.PubMed

93.

Kim YH, Petko Z, Dzieciatkowski S, et al. CpG island methylation of genes accumulates during the adenoma progression step of the multistep pathogenesis of colorectal cancer. Genes Chromosom Cancer. 2006;45:781–789.PubMed

94.

Luo Y, Wong CJ, Kaz AM, et al. Differences in DNA methylation signatures reveal multiple pathways of progression from adenoma to colorectal cancer. Gastroenterology. 2014;147:418–429.

95.

Bettington M, Walker N, Rosty C, et al. Critical appraisal of the diagnosis of the sessile serrated adenoma. Am J Surg Pathol. 2014;38:158–166.PubMed

96.

Leggett B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology. 2010;138:2088–2100.PubMed

97.

Lochhead P, Chan AT, Giovannucci E, et al. Progress and opportunities in molecular pathological epidemiology of colorectal premalignant lesions. Am J Gastroenterol. 2014;109:1205–1214.PubMedCentralPubMed

98.

Shen L, Kondo Y, Hamilton SR, et al. P14 methylation in human colon cancer is associated with microsatellite instability and wild-type p53. Gastroenterology. 2003;124:626–633.PubMed

99.

Luo Y, Yu M, Grady WM. Field cancerization in the colon: a role for aberrant DNA methylation? Gastroenterol Rep (Oxf). 2014;2:16–20.

100.

Worthley DL, Whitehall VL, Buttenshaw RL, et al. DNA methylation within the normal colorectal mucosa is associated with pathway-specific predisposition to cancer. Oncogene. 2010;29:1653–1662.PubMed

101.

Messick CA, Kravochuck S, Church JM, et al. Metachronous serrated neoplasia is uncommon after right colectomy in patients with methylator colon cancers with a high degree of microsatellite instability. Dis Colon Rectum. 2014;57:39–46.PubMed

102.

Shen L, Kondo Y, Rosner GL, et al. MGMT promoter methylation and field defect in sporadic colorectal cancer. J Natl Cancer Inst. 2005;97:1330–1338.PubMed

103.

Ahuja N, Li Q, Mohan M, et al. Aging and DNA methylation in colorectal mucosa and cancer. Cancer Res. 1998;58:5489–5494.PubMed

104.

Maekita T, Nakazawa K, Mihara M, et al. High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res. 2006;12:989–995.PubMed

105.

Rashid A, Shen L, Morris JS, et al. CpG island methylation in colorectal adenomas. Am J Pathol. 2001;159:1129–1135.PubMedCentralPubMed

106.

Braakhuis BJ, Tabor MP, Kummer JA, et al. A genetic explanation of Slaughter’s concept of field cancerization: evidence and clinical implications. Cancer Res. 2003;63:1727–1730.PubMed

107.

Noreen F, Röösli M, Gaj P, et al. Modulation of age- and cancer-associated DNA methylation change in the healthy colon by aspirin and lifestyle. J Natl Cancer Inst. 2014. doi:10.1093/jnci/dju161.

108.

Tapp HS, Commane DM, Bradburn DM, et al. Nutritional factors and gender influence age-related DNA methylation in the human rectal mucosa. Aging Cell. 2013;12:148–155.PubMedCentralPubMed

109.

Hiraoka S, Kato J, Horii J, et al. Methylation status of normal background mucosa is correlated with occurrence and development of neoplasia in the distal colon. Hum Pathol. 2010;41:38–47.PubMed

110.

Kawakami K, Ruszkiewicz A, Bennett G, et al. DNA hypermethylation in the normal colonic mucosa of patients with colorectal cancer. Br J Cancer. 2006;94:593–598.PubMedCentralPubMed

111.

Belshaw NJ, Pal N, Tapp HS, et al. Patterns of DNA methylation in individual colonic crypts reveal aging and cancer-related field defects in the morphologically normal mucosa. Carcinogenesis. 2010;31:1158–1163.PubMed

112.

Grady WM, Parkin RK, Mitchell PS, et al. Epigenetic silencing of the intronic microRNA hsa-miR-342 and its host gene EVL in colorectal cancer. Oncogene. 2008;27:3880–3888.PubMed

113.

Belshaw NJ, Elliott GO, Foxall RJ, et al. Profiling CpG island field methylation in both morphologically normal and neoplastic human colonic mucosa. Br J Cancer. 2008;99:136–142.PubMedCentralPubMed

114.

Paun BC, Kukuruga D, Jin Z, et al. Relation between normal rectal methylation, smoking status, and the presence or absence of colorectal adenomas. Cancer. 2010;116:4495–4501.PubMedCentralPubMed

115.

Kamiyama H, Suzuki K, Maeda T, et al. DNA demethylation in normal colon tissue predicts predisposition to multiple cancers. Oncogene. 2012;31:5029–5037.PubMedCentralPubMed

116.

Xu G, Bestor T, Bourc’his D, et al. Chromosome instability and immunodeficiency syndrome caused by mutations in a DNa methyltransferase gene. Nature. 1999;402:187–189.PubMed

117.

Figueiredo JC, Grau MV, Wallace K, et al. Global DNA hypomethylation (LINE-1) in the normal colon and lifestyle characteristics and dietary and genetic factors. Cancer Epidemiol Biomark Prev. 2009;18:1041–1049.

118.

Wallace K, Grau MV, Levine AJ, et al. Association between folate levels and CpG Island hypermethylation in normal colorectal mucosa. Cancer Prev Res (Phila). 2010;3:1552–1564.

119.

Siena S, Sartore-Bianchi A, Di Nicolantonio F, et al. Biomarkers predicting clinical outcome of epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer. J Natl Cancer Inst. 2009;101(19):1308–1324.

120.

Conesa-Zamora P, Garcia-Solano J, Garcia-Garcia F, et al. Expression profiling shows differential molecular pathways and provides potential new diagnostic biomarkers for colorectal serrated adenocarcinoma. Int J Cancer. 2013;132:297–307.PubMed

121.

Albuquerque C, Baltazar C, Filipe B, et al. Colorectal cancers show distinct mutation spectra in members of the canonical WNT signaling pathway according to their anatomical location and type of genetic instability. Genes Chromosom Cancer. 2010;49:746–759.PubMed

122.

Alhopuro P, Sammalkorpi H, Niittymaki I, et al. Candidate driver genes in microsatellite-unstable colorectal cancer. Int J Cancer. 2012;130:1558–1566.PubMed

123.

Delker DA, McGettigan BM, Kanth P, et al. RNA sequencing of sessile serrated colon polyps identifies differentially expressed genes and immunohistochemical markers. PLoS One. 2014;9:e88367.PubMedCentralPubMed

Titel: The Molecular Pathogenesis of Colorectal Cancer and Its Potential Application to Colorectal Cancer Screening
verfasst von: William M. Grady
Sanford D. Markowitz
Publikationsdatum: 01.03.2015
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 3/2015
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-014-3444-4

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Introduction

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2015

Colonoscopy: The Current King of the Hill in the USA

Blood-Based Tests for Colorectal Cancer Screening: Do They Threaten the Survival of the FIT Test?

A Letter from the National Colorectal Cancer Roundtable

Colon PillCam: Why Not Just Take a Pill?

Do Recent Epidemiologic Observations Impact Who and How We Should Screen for CRC?