Epigenetic silencing of SMOC1 in traditional serrated adenoma and colorectal cancer.
Epigenetic silencing of SMOC1 in traditional serrated adenoma and colorectal cancer.
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DOI：
10.18632/oncotarget.23523
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发表时间：
2018-01-12
期刊：
影响因子：
--
通讯作者：
Suzuki H
中科院分区：
文献类型：
--
作者：
Aoki H;Yamamoto E;Takasawa A;Niinuma T;Yamano HO;Harada T;Matsushita HO;Yoshikawa K;Takagi R;Harada E;Tanaka Y;Yoshida Y;Aoyama T;Eizuka M;Yorozu A;Kitajima H;Kai M;Sawada N;Sugai T;Nakase H;Suzuki H
结直肠无蒂锯齿状腺瘤/息肉（SSA/Ps）是结直肠癌（CRC）的前体，其特征在于BRAF突变和微卫星不稳定性。相比之下，传统的锯齿状腺瘤（TSAs）的分子特征尚未完全了解。我们分析了具有突出和平坦组分的TSA中的全基因组DNA甲基化。我们确定了11个基因，包括SMOC 1，甲基化在TSA的发展过程中逐渐增加。SMOC 1在TSA中预先甲基化，但在SSA/Ps中很少甲基化（p < 0.001）。RT-PCR和免疫组化结果显示，SMOC 1在正常结肠和SSA/Ps中均有表达，而在TSA中表达减弱。SMOC 1的异位表达抑制CRC细胞的增殖、集落形成和体内肿瘤形成。对结直肠病变（n = 847）的分析显示，SMOC 1在TSA、高级别腺瘤和CRC中经常甲基化。其中，SMOC 1甲基化与KRAS突变和CpG岛甲基化表型（CIMP）低密切相关。这些结果表明，表观遗传沉默SMOC 1与TSA的发展，但很少观察到SSA/Ps。因此，SMOC 1表达可能是锯齿状病变的诊断标志物，SMOC 1甲基化可能在TSA和传统腺瘤的肿瘤途径中发挥作用。
Colorectal sessile serrated adenoma/polyps (SSA/Ps) are well-known precursors of colorectal cancer (CRC) characterized by BRAF mutation and microsatellite instability. By contrast, the molecular characteristics of traditional serrated adenoma (TSAs) are not fully understood. We analyzed genome-wide DNA methylation in TSAs having both protruding and flat components. We identified 11 genes, including SMOC1, methylation of which progressively increased during the development of TSAs. SMOC1 was prevalently methylated in TSAs, but was rarely methylated in SSA/Ps (p < 0.001). RT-PCR and immunohistochemistry revealed that SMOC1 was expressed in normal colon and SSA/Ps, but its expression was decreased in TSAs. Ectopic expression of SMOC1 suppressed proliferation, colony formation and in vivo tumor formation by CRC cells. Analysis of colorectal lesions (n = 847) revealed that SMOC1 is frequently methylated in TSAs, high-grade adenomas and CRCs. Among these, SMOC1 methylation was strongly associated with KRAS mutation and CpG island methylator phenotype (CIMP)-low. These results demonstrate that epigenetic silencing of SMOC1 is associated with TSA development but is rarely observed in SSA/Ps. SMOC1 expression could thus be a diagnostic marker of serrated lesions, and SMOC1 methylation could play a role in neoplastic pathways in TSAs and conventional adenomas.
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影响因子：
11.2
作者：
Fackler MJ;Umbricht CB;Williams D;Argani P;Cruz LA;Merino VF;Teo WW;Zhang Z;Huang P;Visvananthan K;Marks J;Ethier S;Gray JW;Wolff AC;Cope LM;Sukumar S
通讯作者：
Sukumar S
大肠癌中的SPARC启动子高甲基化可以被5-Aza-2'deoxyCytidine逆转以增加SPARC表达并改善治疗反应。
影响因子：
8.8
作者：
Cheetham, S.;Tang, M. J.;Mesak, F.;Kennecke, H.;Owen, D.;Tai, I. T.
通讯作者：
Tai, I. T.
影响因子：
16
作者：
Fang, Minggang;Ou, Jianhong;Hutchinson, Lloyd;Green, Michael R.
通讯作者：
Green, Michael R.
影响因子：
29.4
作者：
Leggett, Barbara;Whitehall, Vicki
通讯作者：
Whitehall, Vicki
影响因子：
7.5
作者：
Bettington, Mark L.;Walker, Neal I.;Whitehall, Vicki L. J.
通讯作者：
Whitehall, Vicki L. J.