Dong J T, Chen C, Stultz B G, Isaacs J T, Frierson H F
Department of Pathology, University of Virginia Health System, Charlottesville 22908, USA.
Cancer Res. 2000 Jul 15;60(14):3880-3.
Previous cytogenetic and molecular genetic analyses suggest that the q21 band of chromosome 13 harbors a tumor suppressor gene(s) involved in prostatic carcinogenesis. The precise genetic location, however, has not been defined. In this study, we examined prostate cancer specimens and cell lines/xenograft for genetic deletions at 13q21, using the methods of tissue microdissection and duplex PCR. Deletions at 13q21 were detected in 13 of 147 (9%) prostate cancer samples. Deletion of the same region was also detected in the LNCaP cell line and the PC-82 xenograft of prostate cancer. The overlapping region of deletion in LNCaP and PC-82 spans 3.1 cM or 2.9 cR, which is equivalent to 1-3 Mb. The endothelin receptor B gene, a possible tumor suppressor gene at 13q21, was not located in the region of deletion. Among the 13 prostate neoplasms with deletion at 13q21, 5 were metastases, and 7 were poorly differentiated primary tumors. The only primary tumor that was not poorly differentiated but had deletion occurred in one of the youngest patients (49 years) at diagnosis. These results provide evidence that 13q21 may harbor an unidentified gene(s) whose inactivation occurs in some aggressive carcinomas of the prostate. In addition, this study provides a framework for the cloning and identification of the 13q21 gene(s).
先前的细胞遗传学和分子遗传学分析表明,13号染色体的q21带含有一个参与前列腺癌发生的肿瘤抑制基因。然而,其精确的基因定位尚未明确。在本研究中,我们使用组织显微切割和双重PCR方法,检测前列腺癌标本以及细胞系/异种移植瘤中13q21的基因缺失情况。在147例前列腺癌样本中的13例(9%)检测到13q21的缺失。在LNCaP细胞系和前列腺癌的PC - 82异种移植瘤中也检测到相同区域的缺失。LNCaP和PC - 82中缺失的重叠区域跨度为3.1 cM或2.9 cR,相当于1 - 3 Mb。内皮素受体B基因是13q21上一个可能的肿瘤抑制基因,它并不位于缺失区域。在13例13q21有缺失的前列腺肿瘤中,5例为转移瘤,7例为低分化原发性肿瘤。唯一一例非低分化但有缺失的原发性肿瘤发生在诊断时最年轻的患者(49岁)之一。这些结果证明13q21可能含有一个未被识别的基因,其失活发生在一些侵袭性前列腺癌中。此外,本研究为克隆和鉴定13q21基因提供了一个框架。