Molecular Profiling Based on KRAS/BRAF Mutation, Methylation, and Microsatellite Statuses in Serrated Lesions.
Molecular Profiling Based on KRAS/BRAF Mutation, Methylation, and Microsatellite Statuses in Serrated Lesions.
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DOI：
10.1007/s10620-018-5167-4
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发表时间：
2018-10
影响因子：
3.1
通讯作者：
Matsumoto T
中科院分区：
文献类型：
--
作者：
Sugai T;Eizuka M;Fujita Y;Kawasaki K;Yamamoto E;Ishida K;Yamano H;Suzuki H;Matsumoto T
您的研究目的是根据其分子模式，特别是BRAF/KRAS突变、甲基化和微卫星状态来表征锯齿状病变。我们评估了163例锯齿状病变的分子模式，包括37例微泡性增生性息肉，73例无柄锯齿状腺瘤/息肉（SSA/Ps）， 31例传统锯齿状腺瘤，22例SSA/Ps伴细胞学发育不良/腺癌。BRAF (V600E)/KRAS（外显子2）突变和微卫星状态[微卫星稳定性（MSS vs. MSI）]分别使用焦磷酸测序仪和基于pcr的微卫星方法进行检测。根据基于pcr的两步方法，将DNA甲基化状态分为低（LME）、中（IME）或高甲基化表观基因型（HME）。同时检测粘蛋白和膜联蛋白A10的表达。最后，我们对BRAF/KRAS突变、DNA甲基化和微卫星状态进行了分层聚类分析。在锯齿状病变中观察到的分子模式可分为5个亚组：病变特征为(1)BRAF突变、HME和MSI；(2) BRAF突变、HME和MSS；(3) BRAF突变、LME/IME和MSS；(4)无BRAF/KRAS突变、LME/IME、MSS；(5) KRAS突变、LME/IME和MSS。此外，我们证明了这些观察到的分子模式有助于识别分子模式和标记物（即粘蛋白和膜联蛋白A10）与临床病理结果（包括组织学特征和组织学诊断）的关联。我们认为鉴定的分子模式在锯齿状病变发展的途径中起重要作用。
The aim of your study is to characterize serrated lesions according to their molecular patterns, specifically BRAF/KRAS mutation, methylation, and microsatellite statuses. We evaluated the molecular patterns of 163 serrated lesions, including 37 microvesicular hyperplastic polyps, 73 sessile serrated adenomas/polyps (SSA/Ps), 31 traditional serrated adenomas, and 22 SSA/Ps with cytological dysplasia/adenocarcinoma. Mutations in BRAF (V600E)/KRAS (exon 2) and microsatellite status [microsatellite stability (MSS) vs. MSI] were examined using a pyrosequencer and the PCR-based microsatellite method, respectively. DNA methylation status was classified as low (LME), intermediate (IME), or high methylation epigenotype (HME) according to a PCR-based two-step method. In addition, mucin and annexin A10 expression was examined. Finally, we performed a hierarchical clustering analysis of the BRAF/KRAS mutation, DNA methylation, and microsatellite statuses. The molecular patterns observed in the serrated lesions could be divided into five subgroups: lesions characterized by (1) BRAF mutation, HME, and MSI; (2) BRAF mutation, HME, and MSS; (3) BRAF mutation, LME/IME, and MSS; (4) no BRAF/KRAS mutations, LME/IME, and MSS; and (5) KRAS mutation, LME/IME, and MSS. In addition, we demonstrated that these observed molecular patterns help identify the associations of the molecular patterns and markers (i.e., mucin and annexin A10) with the clinicopathological findings, including histological features and histological diagnosis. We suggest that the identified molecular patterns play an important role in the pathway of serrated lesion development.
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影响因子：
4.3
作者：
Bae, Jeong Mo;Kim, Jung Ho;Kang, Gyeong Hoon
通讯作者：
Kang, Gyeong Hoon
影响因子：
2.4
作者：
Sugai T;Tsukahara M;Endoh M;Shioi Y;Takebe N;Mue Y;Matsushita H;Toyota M;Suzuki K
通讯作者：
Suzuki K
影响因子：
1.2
作者：
Shida, Yosuke;Ichikawa, Kazuhito;Kato, Hiroyuki
通讯作者：
Kato, Hiroyuki
影响因子：
2.8
作者：
Kim, Jung Ho;Rhee, Ye-Young;Kang, Gyeong Hoon
通讯作者：
Kang, Gyeong Hoon
影响因子：
29.4
作者：
Leggett, Barbara;Whitehall, Vicki
通讯作者：
Whitehall, Vicki