Habuchi T, Devlin J, Elder P A, Knowles M A
Molecular Genetics Laboratory, Marie Curie Research Institute, Oxted, Surrey, UK.
Oncogene. 1995 Oct 19;11(8):1671-4.
Loss of heterozygosity (LOH) at loci on chromosome 9p and/or 9q is the most frequent genetic alteration in transitional cell carcinoma (TCC) of the bladder. However, localisation of the tumour suppressor locus or loci on 9q has been hampered by the relative infrequency of tumours with subchromosomal deletions. We have used 24 microsatellite markers to examine LOH in 70 new cases of TCC of the bladder and upper urinary tract. Forty tumours (57%) showed LOH at one or more loci on 9q and partial deletions were detected in five tumours (7%). Combined data from the five cases with partial deletions place one tumour suppressor locus at 9q34 between D9S61 and D9S66 (an estimated distance of 13-14 cM). This region is frequently deleted in other sporadic tumours and encompasses one of the loci for tuberous sclerosis (TSC1). One tumour contained a distinct deletion between D9S153 and D9S109 (9q13-q31), which encompasses the locus for the familial nevoid basal cell carcinoma syndrome (Gorlin syndrome). This may indicate the presence of another tumour suppressor locus on 9q for TCC. Our findings significantly reduce the regions of 9q within which suppressor genes for TCC may reside. The possible involvement of two deletion targets on 9q in addition to the locus at 9p21 implicated in TCC may explain why LOH at all loci on chromosome 9 is frequent in TCC.
9号染色体短臂和/或9号染色体长臂上的杂合性缺失（LOH）是膀胱移行细胞癌（TCC）中最常见的基因改变。然而，9号染色体长臂上肿瘤抑制基因座的定位受到亚染色体缺失肿瘤相对少见的阻碍。我们使用24个微卫星标记检测了70例膀胱及上尿路TCC新病例中的LOH。40个肿瘤（57%）在9号染色体长臂上的一个或多个位点显示出LOH，5个肿瘤（7%）检测到部分缺失。来自5例部分缺失病例的综合数据将一个肿瘤抑制基因座定位在9q34，位于D9S61和D9S66之间（估计距离为13 - 14 cM）。该区域在其他散发性肿瘤中经常缺失，并且包含结节性硬化症（TSC1）的一个基因座。一个肿瘤在D9S153和D9S109之间（9q13 - q31）存在明显缺失，该区域包含家族性痣样基底细胞癌综合征（Gorlin综合征）的基因座。这可能表明9号染色体长臂上存在另一个TCC肿瘤抑制基因座。我们的研究结果显著缩小了9号染色体长臂上可能存在TCC抑制基因的区域。除了9p21位点外，9号染色体长臂上两个缺失靶点可能参与其中，这或许可以解释为什么TCC中9号染色体上所有位点的LOH都很常见。
