Ahman A K, Jonsson B A, Damber J E, Bergh A, Emanuelsson M, Grönberg H
Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
Genes Chromosomes Cancer. 2000 Dec;29(4):292-6. doi: 10.1002/1098-2264(2000)9999:9999<::aid-gcc1038>3.0.co;2-c.
The aim of this study was to investigate allelic imbalance at the major human prostate cancer susceptibility locus HPC1 at 1q24-25 and the recently reported, putative, susceptibility locus at 1p36 in prostate tumors from Swedish families with hereditary prostate cancer. We analyzed 31 prostate tumors and two lymph node metastases from 33 Swedish men in 22 families with hereditary prostate cancer for the presence of allelic imbalance using microsatellite markers D1S158, D1S422, and D1S238 for the HPC1 locus and D1S1597, D1S407, and D1S489 for the 1p36 locus. Frequencies of allelic imbalance at the two investigated loci were quite low, 3 of 27 informative tumors at the 1p36 locus and 3 of 27 informative tumors at the HPC1 locus. Interestingly, two tumors showed allelic imbalance at both loci investigated, suggesting that they may have lost a great part of chromosome 1. Taking this possibility into consideration, the specific loss of the two investigated loci may be even lower (1 of 27 informative tumors for either locus). The very low level of allelic imbalance found at HPC1 and 1p36 makes it unlikely that these loci encode genes that are acting as classic tumor suppressor genes in the initiation or progression of hereditary prostate cancer. Of the eight tumors from HPC1-linked families, only two showed AI at the HPC1 locus, one of which had lost the wild-type allele.
本研究的目的是调查在瑞典遗传性前列腺癌家族的前列腺肿瘤中，位于1q24 - 25的主要人类前列腺癌易感基因座HPC1以及最近报道的位于1p36的假定易感基因座的等位基因失衡情况。我们使用微卫星标记D1S158、D1S422和D1S238检测HPC1基因座，使用D1S1597、D1S407和D1S489检测1p36基因座，分析了来自22个遗传性前列腺癌家族的33名瑞典男性的31个前列腺肿瘤和两个淋巴结转移灶，以检测等位基因失衡情况。在两个研究基因座处，等位基因失衡的频率相当低，在1p36基因座的27个信息性肿瘤中有3个出现失衡，在HPC1基因座的27个信息性肿瘤中有3个出现失衡。有趣的是，有两个肿瘤在两个研究基因座处均显示等位基因失衡，这表明它们可能丢失了1号染色体的很大一部分。考虑到这种可能性，两个研究基因座的特异性缺失可能更低（每个基因座的27个信息性肿瘤中有1个）。在HPC1和1p36处发现的等位基因失衡水平极低，这使得这些基因座不太可能编码在遗传性前列腺癌的发生或发展中起经典肿瘤抑制基因作用的基因。在来自与HPC1连锁家族的8个肿瘤中，只有两个在HPC1基因座处显示等位基因失衡，其中一个丢失了野生型等位基因。
