Gao X, Zacharek A, Grignon D J, Sakr W, Powell I J, Porter A T, Honn K V
Department of Radiation Oncology (Cancer Biology Division), Wayne State University School of Medicine, Detroit, Michigan 48202, USA.
Oncogene. 1995 Oct 5;11(7):1241-7.
We recently demonstrated a high frequency of loss of heterozygosity (LOH) at the D17S856 and D17S855 (within the BRCA1 gene) loci in primary prostate cancer, suggesting that the BRCA1 gene and/or other tumor suppressor gene(s) located within the interval of the D17S856 and D17S855 loci and/or within the vicinity of this interval may be important in prostate cancer (Cancer Res., 55: 1002-1005, 1995). To further define the exact boundary of the deleted region (i.e., D17S856/D17S855) and to detect other possible LOH regions on the long arm of chromosome 17, we analysed 23 matched normal and tumor DNAs with 15 polymorphic microsatellite markers spanning chromosome 17q12-21. Eleven of 22 (50%) informative tumors showed allelic deletion at one or more of the loci studied. A minimal area of LOH was identified to extend from the proximal boundary at the D17S776 locus to the distal boundary at the D17S855 locus, spanning an estimated < 2 Mb segment on chromosome 17q21. Our results suggest that a potential tumor suppressor gene(s) may reside in the < 2 Mb region centromeric (inclusive) to the BRCA1 gene and that this tumor suppressor gene(s) may be involved in the formation of prostate cancer.
我们最近证明,原发性前列腺癌中D17S856和D17S855(位于BRCA1基因内)位点的杂合性缺失(LOH)频率很高,这表明位于D17S856和D17S855位点区间内和/或该区间附近的BRCA1基因和/或其他肿瘤抑制基因可能在前列腺癌中起重要作用(《癌症研究》,55: 1002 - 1005,1995年)。为了进一步确定缺失区域(即D17S856/D17S855)的确切边界,并检测17号染色体长臂上其他可能的LOH区域,我们用跨越17q12 - 21的15个多态微卫星标记分析了23对匹配的正常和肿瘤DNA。22个信息丰富的肿瘤中有11个(50%)在一个或多个研究位点显示等位基因缺失。确定最小的LOH区域从D17S776位点的近端边界延伸到D17S855位点的远端边界,跨越17q21上估计小于2 Mb的片段。我们的结果表明,一个潜在的肿瘤抑制基因可能位于BRCA1基因着丝粒侧(含)的小于2 Mb区域内,并且这个肿瘤抑制基因可能参与前列腺癌的形成。