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berrant CpG island methylation in early-onset sporadic gastricrcinomaurnal Journal of Cancer Research and Clinical Oncology

ublisher Springer Berlin / HeidelbergSN 0171-5216 (Print) 1432-1335 (Online)bject Medicine

sue Volume 131, Number 11 / November, 2005ategory Original PaperOI 10.1007/s00432-005-0017-0ges 733-740

nline DateTuesday, August 02, 2005

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Original Paper

berrant CpG island methylation in early-nset sporadic gastric carcinoma

ee Cheol Kim 1 , Jin Cheon Kim 1,un Ae Roh 1, Chang Sik Yu 1,eong Hwan Yook 1, Sung Tae Oh 1,yung Sik Kim 1, Kun Choon Park 1 and

in Chang2

1) Department of Surgery, University ofUlsan College of Medicine, AsanMedical Center, Asan Medical Center388-1, Pungnap-dong, Songpa-gu,Seoul, Korea

2) Department of Internal Medicine,Kyung Hee University College ofMedicine, Seoul, Korea

eceived: 11 October 2004 Accepted:4 June 2005 Published online:August 2005

bstract Purpose : Gastric carcinomamore commonly affects older patients, and

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is thought that cases of early-onsetastric carcinoma may develop with aifferent molecular profile different fromhat of carcinoma occurring at a later age.

We assayed the methylation status andenetic changes in genes associated withhe APC- -catenin axis and the mismatch

epair system in relatively early-onsetastric carcinoma samples to determineheir association with gastricarcinogenesis. Methods : Tumor andormal tissue DNA samples were obtainedom 40 patients with early-onset (< 50 y)astric carcinomas and assayed for APC nd CTNNB1 mutations, microsatellitenstability, and methylation of the

romoters of the hMLH1, TIMP3, THBS1,AP- K, GSTP1 , APC , and MINT2 .esults : Promoter methylation at theseeven loci ranged from 12.5 to 62%, with8/40 tumors (95%) showing promoter

methylation at more than one locus. ThepG island methylation phenotype (CIMP)as classified as high in 16 tumors (40%),

ow in 22 tumors (55%), and negative in 2

umors (5%). Two concurrent missensemutations (E1685G, R1763L) in the APC mutation cluster region were detected inwo tumors, nine tumors showed loss ofPC heterozygosity (LOH), and twohowed both LOH and promoter

methylation. Conclusions : Our resultsndicate that, unlike in colorectalarcinoma, APC and CTNNB1 mutations

o not appear to be highly implicated inarly-onset gastric carcinogenesis. Inontrast, our data show that promoter

methylation is a prevalent phenomenon inarly-onset gastric carcinoma and may beelated to gastric carcinogenesis.

eywords Stomacheoplasms - Carcinogenesis - Methylation -

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PC - Microsatellite instability

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