IDENTIFICATION OF A GENE LOCATED AT CHROMOSOME-5Q21 THAT IS MUTATED IN COLORECTAL CANCERS
IDENTIFICATION OF A GENE LOCATED AT CHROMOSOME-5Q21 THAT IS MUTATED IN COLORECTAL CANCERS
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DOI：
10.1126/science.1848370
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发表时间：
1991-03-15
期刊：
影响因子：
56.9
通讯作者：
NAKAMURA, Y
中科院分区：
文献类型：
--
作者：
KINZLER, KW;NILBERT, MC;NAKAMURA, Y
最近的研究表明，存在位于染色体5q21区域的抑癌基因。 来自该区域的 DNA 探针被用来研究一组散发性结直肠癌。 其中一种探针，粘粒 5.71，在单个肿瘤的 DNA 中检测到体细胞重排的限制性片段。 对 5.71 粘粒的进一步分析揭示了啮齿动物 DNA 中高度保守的两个区域。 这些序列用于鉴定MCC基因（在结直肠癌中突变），该基因编码829个氨基酸的蛋白质，该蛋白质具有与G蛋白偶联的m3毒蕈碱乙酰胆碱受体相似的一小段区域。 肿瘤中的重排破坏了 MCC 基因的编码区。 此外，在 MCC 中发现两种结直肠肿瘤存在体细胞获得性点突变，导致氨基酸替换。 因此，MCC 是位于 5q21 的假定结直肠肿瘤抑制基因的候选基因。 需要进一步的研究来确定该基因是否在其他散发性肿瘤或具有结肠肿瘤发生遗传倾向的患者的种系中发生突变。
Recent studies have suggested the existence of a tumor suppressor gene located at chromosome region 5q21. DNA probes from this region were used to study a panel of sporadic colorectal carcinomas. One of these probes, cosmid 5.71, detected a somatically rearranged restriction fragment in the DNA from a single tumor. Further analysis of the 5.71 cosmid revealed two regions that were highly conserved in rodent DNA. These sequences were used to identify a gene, MCC (mutated in colorectal cancer), which encodes an 829-amino acid protein with a short region of similarity to the G protein-coupled m3 muscarinic acetylcholine receptor. The rearrangement in the tumor disrupted the coding region of the MCC gene. Moreover, two colorectal tumors were found with somatically acquired point mutations in MCC that resulted in amino acid substitutions. MCC is thus a candidate for the putative colorectal tumor suppressor gene located at 5q21. Further studies will be required to determine whether the gene is mutated in other sporadic tumors or in the germ line of patients with an inherited predisposition to colonic tumorigenesis.