A detailed analysis of the role of K-ras gene mutation in the progression of colorectal adenoma.
A detailed analysis of the role of K-ras gene mutation in the progression of colorectal adenoma.
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K-RAS基因突变在结直肠腺瘤进展中的作用的详细分析。
DOI：
10.1038/bjc.1997.56
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发表时间：
1997
影响因子：
8.8
通讯作者：
Monden, M
中科院分区：
文献类型：
--
作者：
Ohnishi, T;Tomita, N;Monden, T;Ohue, M;Yana, I;Takami, K;Yamamoto, H;Yagyu, T;Kikkawa, N;Shimano, T;Monden, M
为了阐明ras基因突变在结直肠肿瘤进展的早期阶段的作用，K-ras基因突变进行了分析，在32个良性腺瘤和36个腺瘤与局灶性癌在结直肠组织切片，聚合酶链反应-限制性片段长度多态性和部分直接测序的组织学纯区域的显微刮。当腺瘤包含不同程度的发育不良区域时，刮出几个区域并进行分析。K-ras基因突变率在轻度不典型增生、中度不典型增生和局灶性癌中分别为19%（7/36）、51%（25/49）和39%（14/36）。K-ras基因的状态是异质性的11个良性腺瘤，从多个样本中获得的4个，突变总是发现在这些腺瘤中的更先进的不典型增生的区域。36例腺瘤中有13例在腺瘤区和癌灶之间存在异质性突变。其中7例仅在腺瘤区域发生突变。这些结果表明，K-ras基因突变发生在腺瘤进展的晚期阶段，并可能赋予腺瘤更先进的形态表型，但这些突变并不主要参与腺瘤向癌的恶性转化。
To elucidate the role of ras gene mutations during the early stage of colorectal tumour progression, K-ras gene mutations were analysed in 32 benign adenomas and 36 adenomas with focal carcinoma in the colorectum by microscraping of histologically pure regions from tissue sections, polymerase chain reaction-restriction fragment length polymorphism and in part by direct sequencing. Several regions were scraped out and analysed when an adenoma contained areas with different grades of dysplasia. The frequencies of K-ras gene mutation in mild dysplasia, moderate dysplasia and focal carcinoma were 19% (7/36), 51% (25/49) and 39% (14/36) respectively. The K-ras gene status was heterogeneous in 4 of the 11 benign adenomas from which multiple samples were obtained, and mutations were always found in the regions with more advanced dysplasia in these adenomas. Thirteen of the 36 adenomas with focal carcinoma showed heterogeneity of mutations between the adenoma region and the focal carcinoma. Seven of which had mutations only in the adenoma region. These findings indicated that the K-ras gene mutations occur during the late stage of adenoma progression and may confer a more advanced morphological phenotype of adenoma, but these mutations are not mainly involved in malignant transformation from adenoma to carcinoma.