Yeung R S, Buetow K H, Testa J R, Knudson A G
Division of Medical Science, Fox Chase Cancer Center, Philadelphia, PA 19111.
Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8038-42. doi: 10.1073/pnas.90.17.8038.
Germ-line mutations of tumor suppressor genes confer strong predisposition to tumor formation. In the rat, a form of dominantly inherited renal carcinoma (RC) results in multiple chromophobe cell tumors that resemble the human disease, and heterozygous carriers (RC/+) are highly susceptible to environmental agents (radiation and chemical carcinogens), making it a desirable model to study epithelial carcinogenesis. By linkage analysis, the locus of the inherited RC mutation was mapped to rat chromosomal band 10q12, near the protamine locus (logarithm of odds score = 17.96). Renal tumors also showed a loss of heterozygosity at this locus, lending support to the recessive nature of this putative tumor suppressor gene. Our result suggested that the human homolog of the RC gene may reside on human chromosome 16, not known to be altered commonly in human RC.
肿瘤抑制基因的种系突变赋予了肿瘤形成的强烈易感性。在大鼠中,一种显性遗传的肾癌(RC)形式会导致多个嫌色细胞瘤,类似于人类疾病,杂合子携带者(RC/+)对环境因素(辐射和化学致癌物)高度敏感,使其成为研究上皮细胞癌变的理想模型。通过连锁分析,遗传性RC突变的位点被定位到大鼠染色体带10q12,靠近鱼精蛋白位点(优势对数得分=17.96)。肾肿瘤在该位点也显示杂合性缺失,这支持了这个假定的肿瘤抑制基因的隐性性质。我们的结果表明,RC基因的人类同源物可能位于人类16号染色体上,而在人类肾癌中该染色体通常未发生改变。