Assessment of epigenetic alterations in early colorectal lesions containing BRAF mutations.
Assessment of epigenetic alterations in early colorectal lesions containing BRAF mutations.
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DOI：
10.18632/oncotarget.9044
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发表时间：
2016-06-07
期刊：
影响因子：
--
通讯作者：
Suzuki H
中科院分区：
文献类型：
--
作者：
Sawada T;Yamamoto E;Yamano HO;Nojima M;Harada T;Maruyama R;Ashida M;Aoki H;Matsushita HO;Yoshikawa K;Harada E;Tanaka Y;Wakita S;Niinuma T;Kai M;Eizuka M;Sugai T;Suzuki H
为了阐明结直肠锯齿状病变的分子和临床病理学特征，我们评估了来自94名个体的BRAF突变癌前病变队列中癌症相关基因的DNA甲基化。然后将这些结果与病变的临床病理特征，特别是结直肠亚部位进行比较。其中增生性息肉16例，传统型锯齿状腺瘤15例，锯齿状腺瘤伴无蒂型锯齿状腺瘤6例，锯齿状腺瘤49例，锯齿状腺瘤伴异型增生16例。乙状结肠和直肠中表现出CpG岛甲基化表型（CIMP）的病变患病率低于其他肠亚部位，包括盲肠、升结肠、横结肠和降结肠。此外，几个癌症相关基因在乙状结肠近端病变内的甲基化水平高于乙状结肠和直肠。这些结果表明，BRAF突变病变的甲基化状态与其位置，组织学表现和肿瘤途径密切相关。相比之下，在正常外观的背景结肠粘膜沿着肠亚位点中未观察到异常DNA甲基化的差异，这可能表明不存在表观遗传场缺陷。
To clarify the molecular and clinicopathological characteristics of colorectal serrated lesions, we assessed the DNA methylation of cancer-associated genes in a cohort of BRAF-mutant precancerous lesions from 94 individuals. We then compared those results with the lesions' clinicopathological features, especially colorectal subsites. The lesions included hyperplastic polyps (n = 16), traditional serrated adenomas (TSAs) (n = 15), TSAs with sessile serrated adenomas (SSAs) (n = 6), SSAs (n = 49) and SSAs with dysplasia (n = 16). The prevalence of lesions exhibiting the CpG island methylator phenotype (CIMP) was lower in the sigmoid colon and rectum than in other bowel subsites, including the cecum, ascending, transverse and descending colon. In addition, several cancer-associated genes showed higher methylation levels within lesions in the proximal to sigmoid colon than in the sigmoid colon and rectum. These results indicate that the methylation status of lesions with BRAF mutation is strongly associated with their location, histological findings and neoplastic pathways. By contrast, no difference in aberrant DNA methylation was observed in normal-appearing background colonic mucosa along the bowel subsites, which may indicate the absence of an epigenetic field defect.
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影响因子：
9.8
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Farraye, Francis A.
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11.2
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影响因子：
6.4
作者：
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通讯作者：
Suzuki, Kazuyuki
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.