Skip to main content
Erschienen in: Virchows Archiv 6/2015

01.06.2015 | Original Article

Prognostic significance of promoter CpG island hypermethylation and repetitive DNA hypomethylation in stage I lung adenocarcinoma

verfasst von: Ye-Young Rhee, Tae-Hun Lee, Young Seok Song, Xianyu Wen, Hyojin Kim, Sanghoon Jheon, Choon-Taek Lee, Jei Kim, Nam-Yun Cho, Jin Haeng Chung, Gyeong Hoon Kang

Erschienen in: Virchows Archiv | Ausgabe 6/2015

Einloggen, um Zugang zu erhalten

Abstract

In carcinogenesis of peripheral pulmonary carcinomas, multiple genetic and epigenetic alterations are involved. In this study, we quantified methylation levels of repetitive DNA elements (L1 and Alu) and six CpG island methylator phenotype (CIMP)-panel markers in various lesions representing steps in the development of lung adenocarcinoma (ADC), including atypical adenomatous hyperplasia, adenocarcinoma in situ, and invasive ADC. We then assessed methylation levels in an independent set of stage I ADCs (n = 100) and correlated methylation status with clinicopathological findings and clinical outcome. The pattern of changes in the methylation levels of L1 and Alu was different during progression of the lesion along the process of multistep carcinogenesis. A methylation level of >52.4 % of L1 and of >19.7 % of Alu in stage I ADC was associated with shorter cancer-specific survival in univariate but not in multivariate analysis. A tumor to normal lung tissue methylation ratio of >0.693 of L1 was an independent parameter heralding poor prognosis for stage I ADC patients. Methylation of CIMP-related genes was found in ADC. Stage I ADC cases without methylation of any of the six markers had a significantly shorter cancer-specific survival than ADC with methylation of one or more markers. The combination of tumor to normal L1 methylation ratio > 0.693 and absence of methylation of CIMP markers correlated independently with shorter cancer-specific survival. In conclusion, our findings suggest that Alu hypomethylation is an early and L1 hypomethylation a later event during multistep pulmonary carcinogenesis. The prognostic significance of the combination of methylation status of L1 and CIMP markers must be validated in large-scale studies of pulmonary ADC.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
4.
Zurück zum Zitat Ikeda K, Awai K, Mori T, Kawanaka K, Yamashita Y, Nomori H (2007) Differential diagnosis of ground-glass opacity nodules: CT number analysis by three-dimensional computerized quantification. Chest 132:984–990. doi:10.1378/chest. 07-0793 PubMedCrossRef Ikeda K, Awai K, Mori T, Kawanaka K, Yamashita Y, Nomori H (2007) Differential diagnosis of ground-glass opacity nodules: CT number analysis by three-dimensional computerized quantification. Chest 132:984–990. doi:10.​1378/​chest.​ 07-0793 PubMedCrossRef
7.
Zurück zum Zitat Yoo SB, Chung JH, Lee HJ, Lee CT, Jheon S, Sung SW (2010) Epidermal growth factor receptor mutation and p53 overexpression during the multistage progression of small adenocarcinoma of the lung. J Thorac Oncol 5:964–969. doi:10.1097/JTO.0b013e3181dd15c0 PubMed Yoo SB, Chung JH, Lee HJ, Lee CT, Jheon S, Sung SW (2010) Epidermal growth factor receptor mutation and p53 overexpression during the multistage progression of small adenocarcinoma of the lung. J Thorac Oncol 5:964–969. doi:10.​1097/​JTO.​0b013e3181dd15c0​ PubMed
8.
Zurück zum Zitat Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann N, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie WR, de la Bastide M, Dedhia N, Blocker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey JA, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen HC, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JG, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AF, Stupka E, Szustakowski J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang SP, Yeh RF, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Patrinos A, Morgan MJ, de Jong P, Catanese JJ, Osoegawa K, Shizuya H, Choi S, Chen YJ (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921. doi:10.1038/35057062 PubMedCrossRef Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann N, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie WR, de la Bastide M, Dedhia N, Blocker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey JA, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen HC, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JG, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AF, Stupka E, Szustakowski J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang SP, Yeh RF, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Patrinos A, Morgan MJ, de Jong P, Catanese JJ, Osoegawa K, Shizuya H, Choi S, Chen YJ (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921. doi:10.​1038/​35057062 PubMedCrossRef
9.
Zurück zum Zitat Deininger PL, Moran JV, Batzer MA, Kazazian HH Jr (2003) Mobile elements and mammalian genome evolution. Curr Opin Genet Dev 13:651–658PubMedCrossRef Deininger PL, Moran JV, Batzer MA, Kazazian HH Jr (2003) Mobile elements and mammalian genome evolution. Curr Opin Genet Dev 13:651–658PubMedCrossRef
11.
Zurück zum Zitat Lengauer C, Kinzler KW, Vogelstein B (1997) DNA methylation and genetic instability in colorectal cancer cells. Proc Natl Acad Sci U S A 94:2545–2550PubMedCentralPubMedCrossRef Lengauer C, Kinzler KW, Vogelstein B (1997) DNA methylation and genetic instability in colorectal cancer cells. Proc Natl Acad Sci U S A 94:2545–2550PubMedCentralPubMedCrossRef
12.
Zurück zum Zitat Rodriguez J, Frigola J, Vendrell E, Risques RA, Fraga MF, Morales C, Moreno V, Esteller M, Capella G, Ribas M, Peinado MA (2006) Chromosomal instability correlates with genome-wide DNA demethylation in human primary colorectal cancers. Cancer Res 66:8462–9468. doi:10.1158/0008-5472.CAN-06-0293 PubMedCrossRef Rodriguez J, Frigola J, Vendrell E, Risques RA, Fraga MF, Morales C, Moreno V, Esteller M, Capella G, Ribas M, Peinado MA (2006) Chromosomal instability correlates with genome-wide DNA demethylation in human primary colorectal cancers. Cancer Res 66:8462–9468. doi:10.​1158/​0008-5472.​CAN-06-0293 PubMedCrossRef
13.
Zurück zum Zitat Shinjo K, Okamoto Y, An B, Yokoyama T, Takeuchi I, Fujii M, Osada H, Usami N, Hasegawa Y, Ito H, Hida T, Fujimoto N, Kishimoto T, Sekido Y, Kondo Y (2012) Integrated analysis of genetic and epigenetic alterations reveals CpG island methylator phenotype associated with distinct clinical characters of lung adenocarcinoma. Carcinogenesis 33:1277–1285. doi:10.1093/carcin/bgs154 PubMedCrossRef Shinjo K, Okamoto Y, An B, Yokoyama T, Takeuchi I, Fujii M, Osada H, Usami N, Hasegawa Y, Ito H, Hida T, Fujimoto N, Kishimoto T, Sekido Y, Kondo Y (2012) Integrated analysis of genetic and epigenetic alterations reveals CpG island methylator phenotype associated with distinct clinical characters of lung adenocarcinoma. Carcinogenesis 33:1277–1285. doi:10.​1093/​carcin/​bgs154 PubMedCrossRef
15.
Zurück zum Zitat Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG, Powell CA, Riely GJ, Van Schil PE, Garg K, Austin JH, Asamura H, Rusch VW, Hirsch FR, Scagliotti G, Mitsudomi T, Huber RM, Ishikawa Y, Jett J, Sanchez-Cespedes M, Sculier JP, Takahashi T, Tsuboi M, Vansteenkiste J, Wistuba I, Yang PC, Aberle D, Brambilla C, Flieder D, Franklin W, Gazdar A, Gould M, Hasleton P, Henderson D, Johnson B, Johnson D, Kerr K, Kuriyama K, Lee JS, Miller VA, Petersen I, Roggli V, Rosell R, Saijo N, Thunnissen E, Tsao M, Yankelewitz D (2011) International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma. J Thorac Oncol 6:244–285. doi:10.1097/JTO.0b013e318206a221 PubMedCrossRef Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG, Powell CA, Riely GJ, Van Schil PE, Garg K, Austin JH, Asamura H, Rusch VW, Hirsch FR, Scagliotti G, Mitsudomi T, Huber RM, Ishikawa Y, Jett J, Sanchez-Cespedes M, Sculier JP, Takahashi T, Tsuboi M, Vansteenkiste J, Wistuba I, Yang PC, Aberle D, Brambilla C, Flieder D, Franklin W, Gazdar A, Gould M, Hasleton P, Henderson D, Johnson B, Johnson D, Kerr K, Kuriyama K, Lee JS, Miller VA, Petersen I, Roggli V, Rosell R, Saijo N, Thunnissen E, Tsao M, Yankelewitz D (2011) International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma. J Thorac Oncol 6:244–285. doi:10.​1097/​JTO.​0b013e318206a221​ PubMedCrossRef
16.
Zurück zum Zitat Shin SH, Park SY, Ko JS, Kim N, Kang GH (2011) Aberrant CpG island hypermethylation in pediatric gastric mucosa in association with Helicobacter pylori infection. Arch Pathol Lab Med 135:759–765. doi:10.1043/2010-0140-OA.1 PubMed Shin SH, Park SY, Ko JS, Kim N, Kang GH (2011) Aberrant CpG island hypermethylation in pediatric gastric mucosa in association with Helicobacter pylori infection. Arch Pathol Lab Med 135:759–765. doi:10.​1043/​2010-0140-OA.​1 PubMed
17.
Zurück zum Zitat Bae JM, Shin SH, Kwon HJ, Park SY, Kook MC, Kim YW, Cho NY, Kim N, Kim TY, Kim D, Kang GH (2012) ALU and LINE-1 hypomethylations in multistep gastric carcinogenesis and their prognostic implications. Int J Cancer 131:1323–1331. doi:10.1002/ijc.27369 PubMedCrossRef Bae JM, Shin SH, Kwon HJ, Park SY, Kook MC, Kim YW, Cho NY, Kim N, Kim TY, Kim D, Kang GH (2012) ALU and LINE-1 hypomethylations in multistep gastric carcinogenesis and their prognostic implications. Int J Cancer 131:1323–1331. doi:10.​1002/​ijc.​27369 PubMedCrossRef
19.
Zurück zum Zitat O’Brien MJ, Yang S, Mack C, Xu H, Huang CS, Mulcahy E, Amorosino M, Farraye FA (2006) 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 30:1491–1501. doi:10.1097/01.pas.0000213313.36306.85 PubMedCrossRef O’Brien MJ, Yang S, Mack C, Xu H, Huang CS, Mulcahy E, Amorosino M, Farraye FA (2006) 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 30:1491–1501. doi:10.​1097/​01.​pas.​0000213313.​36306.​85 PubMedCrossRef
20.
Zurück zum Zitat Noushmehr H, Weisenberger DJ, Diefes K, Phillips HS, Pujara K, Berman BP, Pan F, Pelloski CE, Sulman EP, Bhat KP, Verhaak RG, Hoadley KA, Hayes DN, Perou CM, Schmidt HK, Ding L, Wilson RK, Van Den Berg D, Shen H, Bengtsson H, Neuvial P, Cope LM, Buckley J, Herman JG, Baylin SB, Laird PW, Aldape K (2010) Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 17:510–522. doi:10.1016/j.ccr.2010.03.017 PubMedCentralPubMedCrossRef Noushmehr H, Weisenberger DJ, Diefes K, Phillips HS, Pujara K, Berman BP, Pan F, Pelloski CE, Sulman EP, Bhat KP, Verhaak RG, Hoadley KA, Hayes DN, Perou CM, Schmidt HK, Ding L, Wilson RK, Van Den Berg D, Shen H, Bengtsson H, Neuvial P, Cope LM, Buckley J, Herman JG, Baylin SB, Laird PW, Aldape K (2010) Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 17:510–522. doi:10.​1016/​j.​ccr.​2010.​03.​017 PubMedCentralPubMedCrossRef
22.
Zurück zum Zitat Kim BH, Cho NY, Shin SH, Kwon HJ, Jang JJ, Kang GH (2009) CpG island hypermethylation and repetitive DNA hypomethylation in premalignant lesion of extrahepatic cholangiocarcinoma. Virchows Arch 455:343–351. doi:10.1007/s00428-009-0829-4 PubMedCrossRef Kim BH, Cho NY, Shin SH, Kwon HJ, Jang JJ, Kang GH (2009) CpG island hypermethylation and repetitive DNA hypomethylation in premalignant lesion of extrahepatic cholangiocarcinoma. Virchows Arch 455:343–351. doi:10.​1007/​s00428-009-0829-4 PubMedCrossRef
23.
Zurück zum Zitat Lee HS, Kim BH, Cho NY, Yoo EJ, Choi M, Shin SH, Jang JJ, Suh KS, Kim YS, Kang GH (2009) Prognostic implications of and relationship between CpG island hypermethylation and repetitive DNA hypomethylation in hepatocellular carcinoma. Clin Cancer Res 15:812–820. doi:10.1158/1078-0432.CCR-08-0266 PubMedCrossRef Lee HS, Kim BH, Cho NY, Yoo EJ, Choi M, Shin SH, Jang JJ, Suh KS, Kim YS, Kang GH (2009) Prognostic implications of and relationship between CpG island hypermethylation and repetitive DNA hypomethylation in hepatocellular carcinoma. Clin Cancer Res 15:812–820. doi:10.​1158/​1078-0432.​CCR-08-0266 PubMedCrossRef
27.
Zurück zum Zitat Iwagami S, Baba Y, Watanabe M, Shigaki H, Miyake K, Ida S, Nagai Y, Ishimoto T, Iwatsuki M, Sakamoto Y, Miyamoto Y, Baba H (2012) Pyrosequencing assay to measure LINE-1 methylation level in esophageal squamous cell carcinoma. Ann Surg Oncol 19:2726–2732. doi:10.1245/s10434-011-2176-3 PubMedCrossRef Iwagami S, Baba Y, Watanabe M, Shigaki H, Miyake K, Ida S, Nagai Y, Ishimoto T, Iwatsuki M, Sakamoto Y, Miyamoto Y, Baba H (2012) Pyrosequencing assay to measure LINE-1 methylation level in esophageal squamous cell carcinoma. Ann Surg Oncol 19:2726–2732. doi:10.​1245/​s10434-011-2176-3 PubMedCrossRef
28.
Zurück zum Zitat Ohka F, Natsume A, Motomura K, Kishida Y, Kondo Y, Abe T, Nakasu Y, Namba H, Wakai K, Fukui T, Momota H, Iwami K, Kinjo S, Ito M, Fujii M, Wakabayashi T (2011) The global DNA methylation surrogate LINE-1 methylation is correlated with MGMT promoter methylation and is a better prognostic factor for glioma. PLoS ONE 6:e23332. doi:10.1371/journal.pone.0023332 PubMedCentralPubMedCrossRef Ohka F, Natsume A, Motomura K, Kishida Y, Kondo Y, Abe T, Nakasu Y, Namba H, Wakai K, Fukui T, Momota H, Iwami K, Kinjo S, Ito M, Fujii M, Wakabayashi T (2011) The global DNA methylation surrogate LINE-1 methylation is correlated with MGMT promoter methylation and is a better prognostic factor for glioma. PLoS ONE 6:e23332. doi:10.​1371/​journal.​pone.​0023332 PubMedCentralPubMedCrossRef
29.
Zurück zum Zitat Sigalotti L, Fratta E, Bidoli E, Covre A, Parisi G, Colizzi F, Coral S, Massarut S, Kirkwood JM, Maio M (2011) Methylation levels of the "long interspersed nucleotide element-1" repetitive sequences predict survival of melanoma patients. J Transl Med 9:78. doi:10.1186/1479-5876-9-78 PubMedCentralPubMedCrossRef Sigalotti L, Fratta E, Bidoli E, Covre A, Parisi G, Colizzi F, Coral S, Massarut S, Kirkwood JM, Maio M (2011) Methylation levels of the "long interspersed nucleotide element-1" repetitive sequences predict survival of melanoma patients. J Transl Med 9:78. doi:10.​1186/​1479-5876-9-78 PubMedCentralPubMedCrossRef
30.
Zurück zum Zitat Saito K, Kawakami K, Matsumoto I, Oda M, Watanabe G, Minamoto T (2010) Long interspersed nuclear element 1 hypomethylation is a marker of poor prognosis in stage IA non-small cell lung cancer. Clin Cancer Res 16:2418–2426. doi:10.1158/1078-0432.CCR-09-2819 PubMedCrossRef Saito K, Kawakami K, Matsumoto I, Oda M, Watanabe G, Minamoto T (2010) Long interspersed nuclear element 1 hypomethylation is a marker of poor prognosis in stage IA non-small cell lung cancer. Clin Cancer Res 16:2418–2426. doi:10.​1158/​1078-0432.​CCR-09-2819 PubMedCrossRef
32.
Zurück zum Zitat Shigaki H, Baba Y, Watanabe M, Iwagami S, Miyake K, Ishimoto T, Iwatsuki M, Baba H (2012) LINE-1 hypomethylation in noncancerous esophageal mucosae is associated with smoking history. Ann Surg Oncol 19:4238–4243. doi:10.1245/s10434-012-2488-y PubMedCrossRef Shigaki H, Baba Y, Watanabe M, Iwagami S, Miyake K, Ishimoto T, Iwatsuki M, Baba H (2012) LINE-1 hypomethylation in noncancerous esophageal mucosae is associated with smoking history. Ann Surg Oncol 19:4238–4243. doi:10.​1245/​s10434-012-2488-y PubMedCrossRef
33.
Zurück zum Zitat Liu F, Killian JK, Yang M, Walker RL, Hong JA, Zhang M, Davis S, Zhang Y, Hussain M, Xi S, Rao M, Meltzer PA, Schrump DS (2010) Epigenomic alterations and gene expression profiles in respiratory epithelia exposed to cigarette smoke condensate. Oncogene 29:3650–3664. doi:10.1038/onc.2010.129 PubMedCrossRef Liu F, Killian JK, Yang M, Walker RL, Hong JA, Zhang M, Davis S, Zhang Y, Hussain M, Xi S, Rao M, Meltzer PA, Schrump DS (2010) Epigenomic alterations and gene expression profiles in respiratory epithelia exposed to cigarette smoke condensate. Oncogene 29:3650–3664. doi:10.​1038/​onc.​2010.​129 PubMedCrossRef
35.
Zurück zum Zitat Zhang FF, Cardarelli R, Carroll J, Fulda KG, Kaur M, Gonzalez K, Vishwanatha JK, Santella RM, Morabia A (2011) Significant differences in global genomic DNA methylation by gender and race/ethnicity in peripheral blood. Epigenetics 6:623–629PubMedCentralPubMedCrossRef Zhang FF, Cardarelli R, Carroll J, Fulda KG, Kaur M, Gonzalez K, Vishwanatha JK, Santella RM, Morabia A (2011) Significant differences in global genomic DNA methylation by gender and race/ethnicity in peripheral blood. Epigenetics 6:623–629PubMedCentralPubMedCrossRef
Metadaten
Titel
Prognostic significance of promoter CpG island hypermethylation and repetitive DNA hypomethylation in stage I lung adenocarcinoma
verfasst von
Ye-Young Rhee
Tae-Hun Lee
Young Seok Song
Xianyu Wen
Hyojin Kim
Sanghoon Jheon
Choon-Taek Lee
Jei Kim
Nam-Yun Cho
Jin Haeng Chung
Gyeong Hoon Kang
Publikationsdatum
01.06.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Virchows Archiv / Ausgabe 6/2015
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-015-1749-0

Weitere Artikel der Ausgabe 6/2015

Virchows Archiv 6/2015 Zur Ausgabe

Editorial

In this issue

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Open Access Biomarker Leitthema

Um auch an kleinen Gewebeproben zuverlässige und reproduzierbare Ergebnisse zu gewährleisten ist eine strenge Qualitätskontrolle in jedem Schritt des Arbeitsablaufs erforderlich. Eine nicht ordnungsgemäße Prüfung oder Behandlung des …

Vergleichende Pathologie in der onkologischen Forschung

Pathologie Leitthema

Die vergleichende experimentelle Pathologie („comparative experimental pathology“) ist ein Fachbereich an der Schnittstelle von Human- und Veterinärmedizin. Sie widmet sich der vergleichenden Erforschung von Gemeinsamkeiten und Unterschieden von …

Gastrointestinale Stromatumoren

Open Access GIST CME-Artikel

Gastrointestinale Stromatumoren (GIST) stellen seit über 20 Jahren ein Paradigma für die zielgerichtete Therapie mit Tyrosinkinaseinhibitoren dar. Eine elementare Voraussetzung für eine mögliche neoadjuvante oder adjuvante Behandlung bei …

Personalisierte Medizin in der Onkologie

Aufgrund des erheblichen technologischen Fortschritts in der molekularen und genetischen Diagnostik sowie zunehmender Erkenntnisse über die molekulare Pathogenese von Krankheiten hat in den letzten zwei Jahrzehnten ein grundlegender …