Latil A, Cussenot O, Fournier G, Baron J C, Lidereau R
Laboratoire d'Oncogénétique, Centre René Huguenin, 5 rue Gaston Latouche, F-92211 St-Cloud, France.
Clin Cancer Res. 1995 Nov;1(11):1385-9.
It is widely accepted that an accumulation of genetic alterations plays an important role in the genesis of human cancers, but little is known about prostate cancer in this respect. Recent studies have identified regions on chromosome arms 8p, 10q, 16q, and 18q that are frequently deleted in human prostate cancer. We have previously described a loss of heterozygosity (LOH) at the Met locus on chromosome band 7q31 in a study of 20 localized prostate tumors. To determine whether a region on the 7q arm is important in the initiation and/or progression of prostate cancer, prostate tissue from 13 patients with confined prostate tumors, 17 with local extracapsular extension, and 13 with metastatic forms were analyzed for LOH, using a DNA probe for RFLP (pMetH) and 8 CA microsatellite repeats (7 on 7q21-q33 and 1 on 7p). Twenty (47%) of the 43 cases studied showed LOH at one or more 7q loci. The most frequently deleted region was chromosome 7q31.1-7q31.2, whereas the centromeric locus on 7q21 was generally conserved. The percentage of LOH was normally distributed around the D7S480 locus. Moreover, the rate of LOH in the 7q31 region was lower in metastatic tumors than in localized tumors. These results strongly suggest the presence of a tumor suppressor gene on the chromosome band 7q31 with an important role in the early stages of prostate cancer.
人们普遍认为,基因改变的积累在人类癌症的发生中起着重要作用,但在这方面对前列腺癌的了解却很少。最近的研究已经确定了染色体臂8p、10q、16q和18q上的区域,这些区域在人类前列腺癌中经常缺失。在一项对20例局限性前列腺肿瘤的研究中,我们之前曾描述过染色体带7q31上Met位点的杂合性缺失(LOH)。为了确定7q臂上的一个区域在前列腺癌的起始和/或进展中是否重要,我们使用用于RFLP的DNA探针(pMetH)和8个CA微卫星重复序列(7个在7q21 - q33上,1个在7p上),对13例局限性前列腺肿瘤患者、17例局部包膜外扩展患者和13例转移型患者的前列腺组织进行了LOH分析。在研究的43例病例中,有20例(47%)在一个或多个7q位点显示出LOH。最常缺失的区域是染色体7q31.1 - 7q31.2,而7q21上的着丝粒位点通常是保守的。LOH的百分比在D7S480位点周围呈正态分布。此外,7q31区域的LOH发生率在转移瘤中低于局限性肿瘤。这些结果强烈表明染色体带7q31上存在一个肿瘤抑制基因,它在前列腺癌的早期阶段起着重要作用。