Webb G C, Jenkins N A, Largaespada D A, Copeland N G, Fernandez C S, Bowtell D D
Department of Genetics, Queen Elizabeth Hospital, Woodville, Australia.
Genomics. 1993 Oct;18(1):14-9. doi: 10.1006/geno.1993.1421.
Activating mutations in the ras genes are commonly found in a wide range of human tumors. We recently cloned two mammalian genes, Son of sevenless 1 (mSos1) and Son of sevenless 2 (mSos2), whose protein products appear to be important positive regulators of ras proteins. Given the proposed role of Sos proteins in ras regulation, and the frequent occurrence of activated ras alleles in tumor cells, we were interested in determining whether the Sos genes may also be activated inappropriately by DNA rearrangement in tumor cells. To investigate this possibility, we have determined the chromosomal locations of both the mouse and the human Sos1 and Sos2 genes, using a combination of genetic linkage analysis and in situ hybridization to chromosomal spreads. We find that the murine Sos1 and Sos2 genes map to chromosomes 17E and 12C3.3-D and their human counterparts to chromosomes 2p21-2p2 and 14q21, respectively. Neither the human nor the mouse Sos loci map close to known mutations or to regions showing consistent karyotypic abnormalities in tumor cells.
ras基因中的激活突变常见于多种人类肿瘤中。我们最近克隆了两个哺乳动物基因,七号less之子1(mSos1)和七号less之子2(mSos2),其蛋白质产物似乎是ras蛋白重要的正向调节因子。鉴于Sos蛋白在ras调节中的假定作用,以及肿瘤细胞中活化ras等位基因的频繁出现,我们有兴趣确定Sos基因是否也可能因肿瘤细胞中的DNA重排而被不适当激活。为了研究这种可能性,我们结合遗传连锁分析和染色体涂片原位杂交技术,确定了小鼠和人类Sos1和Sos2基因的染色体位置。我们发现,小鼠的Sos1和Sos2基因分别定位于17E染色体和12C3.3 - D染色体,而它们在人类中的对应基因分别定位于2p21 - 2p2染色体和14q21染色体。人类和小鼠的Sos基因座均未定位于靠近已知突变或肿瘤细胞中显示一致核型异常的区域。