MUTATIONS IN THE KRAS2 ONCOGENE DURING PROGRESSIVE STAGES OF HUMAN-COLON CARCINOMA
MUTATIONS IN THE KRAS2 ONCOGENE DURING PROGRESSIVE STAGES OF HUMAN-COLON CARCINOMA
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DOI：
10.1073/pnas.86.7.2403
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发表时间：
1989-04-01
影响因子：
11.1
通讯作者：
LOEB, LA
中科院分区：
文献类型：
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作者：
BURMER, GC;LOEB, LA
分析了一系列结肠癌、腺瘤和结肠组织的倍性改变和KRAS 2突变。为了提高识别突变的灵敏度，我们使用了组织学富集、细胞分选和通过聚合酶催化的链式反应进行DNA扩增，然后进行直接DNA序列分析。在分析的40个癌中，27个含有非整倍体细胞，26个含有KRAS 2密码子12的第一个位置的突变。在研究的12个腺瘤中，4个含有非整倍体细胞，9个在密码子12处含有相同的突变。在腺瘤和癌中，在二倍体和非整倍体细胞中均鉴定出突变。在某些情况下，组织学良性粘膜癌附近的区域包含突变。这些综合结果表明，KRAS 2突变发生在人类结肠癌发展的早期，倍性变化之前，这些突变存在于二倍体细胞中，由此产生非整倍体亚群。此外，突变可能存在于癌旁组织学正常的粘膜中，这表明这些肿瘤周围可能存在遗传异常的粘膜。
A series of colon carcinomas, adenomas, and ajacent tissues were analyzed for ploidy alterations and mutations in KRAS2. To incrase the sensitivity for identifying mutations, we used histological enrichment, cell sorting, and DNA amplification by the polymerase-catalyzed chain reaction followed by direct DNA sequence analysis. Of the 40 carcinomas analyzed, 27 contained aneuploid cells and 26 contained mutations at the first position of codon 12 of KRAS2. Of the 12 adenomas studied, 4 contained aneuploid cells and 9 contained the same mutation at codon 12. In both adenomas and carcinomas, mutations were identified in both diploid and aneuploid cells. In some cases, regions of histologically benign mucosa adjacent to the carcinoma contained mutations. These combined results suggest that mutations in KRAS2 occur early in the development of human colon carcinoma, before change in ploidy, and that these mutations exist in diploid cells from which an aneuploid subpopulation arises. Furthermore, mutations may exist in histologically normal mucosa in regions adjacent to carcinoma, suggesting that a field of genetically abnormal mucosa may surround these tumors.