Open AccessJournal Article
Aberrant Methylation in Gastric Cancer Associated with the CpG Island Methylator Phenotype
Minoru Toyota,Nita Ahuja,Hiromu Suzuki,Fumio Itoh,Mutsumi Ohe-Toyota,Kohzoh Imai,Stephen B. Baylin,Jean Pierre J. Issa,Jean Pierre J. Issa +8 more
TLDR
The methylation status of five newly cloned CpG islands was examined in 56 gastric cancers and it is suggested that CIMP may be one of the major pathways that contribute to tumorigenesis in Gastric cancers.Abstract:
Aberrant methylation of 5' CpG islands is thought to play an important role in the inactivation of tumor suppressor genes in cancer. In colorectal cancer, a group of tumors is characterized by a hypermethylator phenotype termed CpG island methylator phenotype (CIMP), which includes methylation of such genes as p16 and hMLH1. To study whether CIMP is present in gastric cancer, the methylation status of five newly cloned CpG islands was examined in 56 gastric cancers using bisulfite-PCR. Simultaneous methylation of three loci or more was observed in 23 (41%) of 56 cancers, which suggests that these tumors have the hypermethylator phenotype CIMP. There was a significant concordance between CIMP and the methylation of known genes including p16, and hMLH1; methylation of p16 was detected in 16 (70%) of 23 CIMP+ tumors, 1 (8%) of 12 CIMP intermediate tumors, and 1 (5%) of 21 CIMP- tumors (P<0.0001). Methylation of the hMLH1 gene was detected in three of five tumors that showed microsatellite instability, and all three of the cases were CIMP+. The CIMP phenotype is an early event in gastric cancer, being present in the normal tissue adjacent to cancer in 5 of 56 cases. These results suggest that CIMP may be one of the major pathways that contribute to tumorigenesis in gastric cancers.read more
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Journal ArticleDOI
Comprehensive molecular characterization of gastric adenocarcinoma
Adam J. Bass,Vesteinn Thorsson,Ilya Shmulevich,Sheila Reynolds,Michael Miller,Brady Bernard,Toshinori Hinoue,Peter W. Laird,Christina Curtis,Hui Shen,Daniel J. Weisenberger,Nikolaus Schultz,Ronglai Shen,Nils Weinhold,David P. Kelsen,Reanne Bowlby,Andy Chu,Katayoon Kasaian,Andrew J. Mungall,A. Gordon Robertson,Payal Sipahimalani,Andrew D. Cherniack,Gad Getz,Yingchun Liu,Michael S. Noble,Chandra Pedamallu,Carrie Sougnez,Amaro Taylor-Weiner,Rehan Akbani,Ju Seog Lee,Wenbin Liu,GB Mills,Da Yang,Wei Zhang,Angeliki Pantazi,Michael Parfenov,Margaret L. Gulley,M. Blanca Piazuelo,Barbara G. Schneider,Jihun Kim,Alex Boussioutas,Margi Sheth,John A. Demchok,Charles S. Rabkin,Joseph Willis,Sam Ng,Katherine S. Garman,David G. Beer,Arjun Pennathur,Benjamin J. Raphael,Hsin-Ta Wu,Robert D. Odze,Hark Kyun Kim,Jay Bowen,Kristen M. Leraas,Tara M. Lichtenberg,Stephanie Weaver,Michael D. McLellan,Maciej Wiznerowicz,Ryo Sakai,Michael S. Lawrence,Kristian Cibulskis,Lee Lichtenstein,Sheila Fisher,Stacey Gabriel,Eric S. Lander,Li Ding,Beifang Niu,Adrian Ally,Miruna Balasundaram,Inanc Birol,Denise Brooks,Yaron S.N. Butterfield,Rebecca Carlsen,Justin Chu,Eric Chuah,Hye Jung E. Chun,Amanda Clarke,Noreen Dhalla,Ranabir Guin,Robert A. Holt,Steven J.M. Jones,Darlene Lee,Haiyan A. Li,Emilia L. Lim,Yussanne Ma,Marco A. Marra,Michael Mayo,Richard A. Moore,Karen Mungall,Ka Ming Nip,Jacqueline E. Schein,Angela Tam,Nina Thiessen,Rameen Beroukhim,Scott L. Carter,Andrew D. Cherniack,Juok Cho,Daniel DiCara,Scott Frazer,Nils Gehlenborg,David I. Heiman,Joonil Jung,Jaegil Kim,Pei Lin,Matthew Meyerson,Akinyemi I. Ojesina,Chandra Sekhar Pedamallu,Gordon Saksena,Steven E. Schumacher,Petar Stojanov,Barbara Tabak,Doug Voet,Mara Rosenberg,Travis I. Zack,Hailei Zhang,Lihua Zou,Alexei Protopopov,Netty Santoso,Semin Lee,Jianhua Zhang,Harshad S. Mahadeshwar,Jiabin Tang,Xiaojia Ren,Sahil Seth,Lixing Yang,Andrew Wei Xu,Xingzhi Song,Ruibin Xi,Christopher A. Bristow,Angela Hadjipanayis,Jonathan G. Seidman,Lynda Chin,Peter J. Park,Raju Kucherlapati,Shiyun Ling,Arvind Rao,John N. Weinstein,Sang Bae Kim,Yiling Lu,Gordon B. Mills,Moiz S. Bootwalla,Phillip H. Lai,Timothy J. Triche,David Van Den Berg,Stephen B. Baylin,James G. Herman,Bradley A. Murray,B. Arman Askoy,Giovanni Ciriello,Gideon Dresdner,Jianjiong Gao,Benjamin Gross,Anders Jacobsen,William Lee,Ricardo Ramirez,Chris Sander,Yasin Senbabaoglu,Rileen Sinha,S. Onur Sumer,Yichao Sun,Lisa Iype,Roger Kramer,Richard Kreisberg,Hector Rovira,Natalie Tasman,Santa Cruz Sam Ng,David Haussler,Josh Stuart,Roeland Verhaak,Mark D.M. Leiserson,Barry S. Taylor,Aaron D. Black,Julie Ann Carney,Julie M. Gastier-Foster,Carmen Helsel,Cynthia McAllister,Nilsa C. Ramirez,Teresa R. Tabler,Lisa Wise,Erik Zmuda,Robert Penny,Daniel Crain,Johanna Gardner,Kevin Lau,Erin Curely,David Mallery,Scott Morris,Joseph Paulauskis,Troy Shelton,Candace Shelton,Mark E. Sherman,Christopher C. Benz,Jae Hyuk Lee,Konstantin V. Fedosenko,Georgy Manikhas,Olga Potapova,Olga Voronina,Smitry Belyaev,Oleg Dolzhansky,W. Kimryn Rathmell,Jakub Brzezinski,Matthew Ibbs,Konstanty Korski,Witold Kycler,Radoslaw ŁaŸniak,Ewa Leporowska,Andrzej Mackiewicz,Dawid Murawa,Pawel Murawa,Arkadiusz Spychała,Wiktoria Maria Suchorska,Honorata Tatka,M. Teresiak,Raafat Abdel-Misih,Joseph J. Bennett,Jennifer Brown,Mary Iacocca,Brenda Rabeno,Sun Young Kwon,Ariane Kemkes,Erin Curley,Iakovina Alexopoulou,Jay Engel,John M. S. Bartlett,Monique Albert,Do-Youn Park,Rajiv Dhir,James D. Luketich,Rodney J. Landreneau,Yelena Y. Janjigian,Eunjung Cho,Marc Ladanyi,Laura H. Tang,Shannon J. McCall,Young Soo Park,Jae Ho Cheong,Jaffer A. Ajani,M. Constanza Camargo,Shelley Alonso,Brenda Ayala,Mark A. Jensen,Todd Pihl,Rohini Raman,Jessica Walton,Yunhu Wan,Greg Eley,Kenna R. Mills Shaw,Roy Tarnuzzer,Zhining Wang,Liming Yang,Jean C. Zenklusen,Tanja M. Davidsen,Carolyn M. Hutter,Heidi J. Sofia,Robert Burton,Sudha Chudamani,Jia Liu +257 more
TL;DR: A comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project is described and a molecular classification dividing gastric cancer into four subtypes is proposed.
Journal Article
A Gene Hypermethylation Profile of Human Cancer
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CpG island methylator phenotype in cancer
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Journal Article
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Journal ArticleDOI
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Journal ArticleDOI
CpG island methylator phenotype in colorectal cancer.
Minoru Toyota,Nita Ahuja,Mutsumi Ohe-Toyota,James G. Herman,Stephen B. Baylin,Jean Pierre J. Issa +5 more
TL;DR: A pathway in colorectal cancer appears to be responsible for the majority of sporadic tumors with mismatch repair deficiency, and is defined as CpG island methylator phenotype (CIMP); CIMP+ tumors also have a high incidence of p16 and THBS1 methylation, and they include the majority with microsatellite instability related to hMLH 1 methylation.