Mutation of the type II transforming growth factor-beta receptor is coincident with the transformation of human colon adenomas to malignant carcinomas.
Mutation of the type II transforming growth factor-beta receptor is coincident with the transformation of human colon adenomas to malignant carcinomas.
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发表时间：
1998-07
期刊：
影响因子：
11.2
通讯作者：
W. Grady;A. Rajput;L. Myeroff;Dongfeng Liu;K. Kwon;J. Willis;S. Markowitz
中科院分区：
文献类型：
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作者：
W. Grady;A. Rajput;L. Myeroff;Dongfeng Liu;K. Kwon;J. Willis;S. Markowitz
转化生长因子 -β（TGF -β）Ⅱ型受体（RII）是一种结肠癌抑制基因，在通过微卫星不稳定性（MSI）致癌途径产生的90%的人类结肠癌中因突变而失活。为了确定RII突变的病理生理后果，我们测定了其在22个不同阶段的MSI人类结肠腺瘤中出现的时间。在任何早期MSI腺瘤中，包括所有具有单纯管状或绒毛状组织学特征的腺瘤，均未检测到RII突变。检测到的最早的RII突变是在一个高度异型增生区域，但在周围的单纯腺瘤中不存在。另外6个RII突变均在高度进展的腺瘤中发现，这些腺瘤包含明显浸润性腺癌区域。这些RII突变在进展期腺瘤及其相邻的癌区域均被检测到。RII突变是MSI腺瘤中的一个晚期事件，并且与这些腺瘤向癌症的进展密切相关。
The transforming growth factor-beta (TGF-beta) type II receptor (RII) is a colon cancer suppressor gene that is inactivated by mutation in 90% of human colon cancers arising via the microsatellite instability (MSI) pathway of carcinogenesis. To determine the pathophysiological consequence of RII mutations, we have determined the timing of their onset among 22 MSI human colon adenomas of varying stages. No RII mutations were detected in any early MSI adenoma, including all those with simple tubular or villous histology. The earliest RII mutation detected was in a region of high-grade dysplasia but was absent from the surrounding simple adenoma. Six additional RII mutations were all found in highly progressed adenomas that contained regions of frankly invasive adenocarcinoma. These RII mutations were detected in both the advanced adenomas and their adjacent regions of carcinoma. RII mutation is a late event in MSI adenomas and correlates tightly with progression of these adenomas to cancer.