Integrated Analysis of the Endoscopic, Pathological and Molecular Characteristics of Colorectal Tumorigenesis.
Integrated Analysis of the Endoscopic, Pathological and Molecular Characteristics of Colorectal Tumorigenesis.
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结直肠肿瘤发生的内镜、病理和分子特征的综合分析。
DOI：
10.1159/000494410
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Sugai T.
中科院分区：
文献类型：
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作者：
Suzuki H;Yamamoto E;Yamano HO;Nakase H;Sugai T.
结直肠癌（colorectal cancer，CRC）是通过癌基因和抑癌基因的遗传和表观遗传改变的积累而发生的。除了特征良好的腺瘤癌序列，锯齿状瘤形成途径现在被认为是CRC development.SummaryThrough的结肠镜，病理和分子特征的结直肠肿瘤的分析，我们确定了一种新的微表面结构特征的锯齿状病变的替代途径。II型开放（II-O型）小凹模式对无蒂锯齿状腺瘤/息肉（SSA/Ps）具有高度特异性，II-O型阳性肿瘤经常表现出v-raf小鼠肉瘤病毒癌基因同源物B1（BRAF）突变和5′-C-磷酸-G-3′（CpG）岛高甲基化。通过筛选与锯齿状病变发展相关的DNA甲基化，我们检测了传统锯齿状腺瘤（TSAs）中分泌的酸性蛋白和富含半胱氨酸（Cys）相关的模块钙结合1（SMOC 1）的甲基化。SMOC 1的表观遗传沉默在TSA中普遍存在，但在SSA/Ps中很少观察到，这表明SMOC 1可能是锯齿状病变的有用诊断标志物。我们还搜索了与结直肠肿瘤生长模式相关的表观遗传学改变，发现神经降压素受体1甲基化与肿瘤的侧向和非侵袭性生长相关。关键信息通过总结的研究，我们已经能够识别新的形态学和分子特征，有助于更好地了解结直肠肿瘤，提高临床诊断。
BackgroundColorectal cancers (CRCs) develop through the accumulation of genetic and epigenetic alterations of oncogenes and tumor suppressor genes. In addition to the well-characterized adenoma-carcinoma sequence, the serrated neoplasia pathway is now recognized as an alternative pathway for CRC development.SummaryThrough analysis of the colonoscopic, pathological, and molecular features of colorectal tumors, we identified a novel microsurface structure characteristic of serrated lesions. The Type II-Open (Type II-O) pit pattern is highly specific to sessile serrated adenoma/polyps (SSA/Ps), and Type-II-O-positive tumors frequently exhibit v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and 5′-C-phosphate-G-3′(CpG) island hypermethylation. By screening DNA methylation associated with the development of serrated lesions, we detected methylation of secreted protein acidic and rich in cysteine (SPARC)-related modular calcium binding 1 (SMOC1) in traditional serrated adenomas (TSAs). Epigenetic silencing of SMOC1 is prevalent among TSAs but it is rarely observed in SSA/Ps, which suggests SMOC1 could be a useful diagnostic marker of serrated lesions. We also searched for epigenetic alterations associated with the growth pattern of colorectal tumors and found that methylation of neurotensin receptor 1 is associated with lateral and non-invasive tumor growth.Key MessageThrough the summarized studies, we have been able to identify novel morphological and molecular features that could contribute to a better understanding of colorectal tumors and to improved clinical diagnosis.