Afonso A, Emmert-Buck M R, Duray P H, Bostwick D G, Linehan W M, Vocke C D
Urologic Oncology Branch and Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892-1502, USA.
J Urol. 1999 Sep;162(3 Pt 1):922-6. doi: 10.1097/00005392-199909010-00091.
In order to investigate the possible involvement of a tumor suppressor gene(s) on chromosome 13 in prostatic neoplasms, we performed loss of heterozygosity (LOH) analysis on normal and tumor pairs from 36 prostate cancer patients.
Pure DNA was obtained from carcinoma cells and normal epithelium by tissue microdissection. The DNA had previously been analyzed for LOH on chromosomes 8 and 16. After an initial pilot experiment to determine the region(s) of significant LOH from 9 loci on chromosome 13q, 3 loci at and near the Rb1 locus (D13S153, D13S1319, and D13S1303) were chosen for further study.
The overall rate of LOH on chromosome 13 was 27.3%. Four tumors exhibited LOH at all 3 loci. Two tumors exhibited LOH at D13S153 but not at the other, more telomeric loci; two additional tumors had loss at D13S1303 or D13S1319 but not D13S153. These data suggest that a tumor suppressor gene involved in prostate cancer may be located just telomeric to Rb1. Analysis of clinical and pathological data from carcinomas with and without loss shows that chromosome 13q LOH is correlated with advanced stage prostate cancer.
Our LOH data suggests that there may be a tumor suppressor gene telomeric to Rb1 that is potentially involved in prostate cancer progression. Identification of this gene may be valuable in providing diagnostic and prognostic information for prostate cancer patients.
为了研究13号染色体上一个或多个肿瘤抑制基因在前列腺肿瘤中的可能作用，我们对36例前列腺癌患者的正常组织与肿瘤组织配对样本进行了杂合性缺失（LOH）分析。
通过组织显微切割技术从癌细胞和正常上皮细胞中获取纯DNA。这些DNA之前已针对8号和16号染色体上的LOH进行过分析。在初步预实验确定13q染色体上9个位点的显著LOH区域后，选择Rb1位点及其附近的3个位点（D13S153、D13S1319和D13S1303）进行进一步研究。
13号染色体上的总体LOH率为27.3%。4个肿瘤在所有3个位点均表现出LOH。2个肿瘤在D13S153位点表现出LOH，但在其他更靠近端粒的位点未出现；另外2个肿瘤在D13S1303或D13S1319位点出现缺失，但在D13S153位点未出现。这些数据表明，参与前列腺癌的一个肿瘤抑制基因可能位于Rb1基因的端粒侧。对有或无缺失的癌组织的临床和病理数据进行分析表明，13q染色体上的LOH与晚期前列腺癌相关。
我们的LOH数据表明，可能存在一个位于Rb1基因端粒侧的肿瘤抑制基因，它可能参与前列腺癌的进展。鉴定该基因可能对为前列腺癌患者提供诊断和预后信息具有重要价值。
