Cairns P, Tokino K, Eby Y, Sidransky D
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Cancer Res. 1995 Jan 15;55(2):224-7.
To investigate the potential loss of tumor suppressor gene loci on chromosome 9 in human renal cell tumorigenesis we analyzed 42 paired normal and tumor DNAs with 18 polymorphic microsatellite markers spanning this chromosome. Fourteen of 42 (33%) tumors showed partial or complete deletion of chromosome 9. Deletion mapping provided evidence for the presence of a suppressor locus on both the short and long arm of chromosome 9. Homozygous deletion at 9p21-22 in one renal tumor and a selective deletion of distal 9q in another tumor localized the critical regions. The CDKN2/p16 gene was further investigated as a candidate suppressor locus on 9p21-22 by multiplex PCR, Southern analysis, and exon sequencing. We found no additional cases of homozygous deletion nor any rearrangements or point mutations of CDKN2/p16. This is the first report of 9p loss of heterozygosity, homozygous deletion of 9p21-22 and selective deletion of 9q in primary renal cell carcinomas. Understanding the molecular genetic basis of renal cell progression will require the isolation and characterization of additional tumor suppressor genes on chromosome 9.
为了研究人类肾细胞肿瘤发生过程中9号染色体上肿瘤抑制基因位点的潜在缺失情况，我们用跨越该染色体的18个多态性微卫星标记分析了42对正常和肿瘤DNA。42个肿瘤中有14个（33%）显示9号染色体部分或完全缺失。缺失图谱分析为9号染色体短臂和长臂上存在一个抑制基因座提供了证据。一个肾肿瘤中9p21 - 22处的纯合缺失以及另一个肿瘤中9q远端的选择性缺失确定了关键区域。通过多重PCR、Southern分析和外显子测序，进一步研究了CDKN2/p16基因作为9p21 - 22上候选抑制基因座的情况。我们没有发现CDKN2/p16纯合缺失的其他病例，也没有发现任何重排或点突变。这是原发性肾细胞癌中9p杂合性缺失、9p21 - 22纯合缺失和9q选择性缺失的首次报道。了解肾细胞进展的分子遗传基础将需要分离和鉴定9号染色体上的其他肿瘤抑制基因。
