Dunsmuir W D, Edwards S M, Lakhani S R, Young M, Corbishley C, Kirby R S, Dearnaley D P, Dowe A, Ardern-Jones A, Kelly J, Eeles R A
CRC Section of Cancer Genetics and Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey, UK.
Br J Cancer. 1998 Dec;78(11):1430-3. doi: 10.1038/bjc.1998.703.
A recent report has provided strong evidence for a major prostate cancer susceptibility locus (HPC1) on chromosome 1q24-25 (Smith et al, 1996). Most inherited cancer susceptibility genes function as tumour-suppressor genes (TSGs). Allelic loss or imbalance in tumour tissue is often the hallmark of a TSG. Studies of allelic loss have not previously implicated the chromosomal region 1q24-25 in prostate cancer. However, analysis of tumour DNA from cases in prostate cancer families has not been reported. In this study, we have evaluated DNA from tissue obtained from small families [3-5 affected members (n = 17)], sibling pairs (n = 15) and sporadic (n = 40) prostate tumours using the three markers from Smith et al (1996) that defined the maximum multipoint linkage lod score. Although widely spaced (12-50 cM), each marker showed evidence of allelic imbalance in only approximately 7.5% of informative tumours. There was no difference between the familial and sporadic cases. We conclude that the incidence of allelic imbalance at HPC1 is low in both sporadic tumours and small prostate cancer families. In this group of patients, HPC1 is unlikely to be acting as a TSG in the development of prostate cancer.
最近的一份报告提供了强有力的证据,表明1号染色体q24 - 25区域存在一个主要的前列腺癌易感基因座(HPC1)(史密斯等人,1996年)。大多数遗传性癌症易感基因起着肿瘤抑制基因(TSGs)的作用。肿瘤组织中的等位基因缺失或失衡通常是肿瘤抑制基因的标志。以前关于等位基因缺失的研究并未表明1号染色体q24 - 25区域与前列腺癌有关。然而,此前尚未报道对前列腺癌家族病例的肿瘤DNA进行分析。在本研究中,我们使用史密斯等人(1996年)定义最大多点连锁lod分值的三个标记,对来自小家族[3 - 5名患病成员(n = 17)]、同胞对(n = 15)和散发性(n = 40)前列腺肿瘤的组织DNA进行了评估。尽管标记间隔较宽(12 - 50厘摩),但每个标记仅在约7.5%的信息性肿瘤中显示出等位基因失衡的证据。家族性病例和散发性病例之间没有差异。我们得出结论,在散发性肿瘤和小前列腺癌家族中,HPC1处等位基因失衡的发生率都很低。在这组患者中,HPC1在前列腺癌发生过程中不太可能起到肿瘤抑制基因的作用。