Molecular Genetics of Prostate Cancer

为了研究与前列腺癌发生和发展相关的遗传事件，来自国家癌症研究所泌尿外科肿瘤科(UOB)和病理实验室(LOP)的科学家们利用了许多创新的方法，这些方法以从异种组织中获取高纯度的前列腺癌细胞为中心。在LOP中开发了允许这种获取的新型显微切割技术；最新的这种涉及激光捕获细胞的技术极大地提高了解剖的速度和纯度。 染色体缺失通常出现在保护细胞免受癌变的基因附近。使用从99个显微解剖的肿瘤中提取的DNA，UOB的科学家们分析了45个遗传标记，这些标记跨越了一些以前被认为与前列腺癌发生有关的染色体区域。在人类8号染色体上观察到的缺失率最高，总缺失率为86%。大约80%的癌症共有8号染色体(8p21)内的共同缺失区域。该区域还与最近被确定为家族性乳腺癌的区域重叠。 人类前列腺癌被认为在演变为浸润性癌症之前经历了称为前列腺癌上皮内瘤变(PIN)的癌前阶段。在癌中常见的8号染色体缺失区域，63%的PIN病变也存在缺失。这一结果表明，8p21上的异常可能与前列腺癌发生的早期阶段有关。

In order to investigate the genetic events associated with the initiation and progression of prostate cancer, scientists from the Urologic Oncology Branch (UOB) and the Laboratory of Pathology (LOP) at the NCI have made use of a number of innovative methodologies centered around the procurement of highly purified prostatic cancer cells from heterogeneous tissue. Novel microdissection techniques which allow such procurement were developed in the LOP; the most recent such technique involving laser capture of cells greatly increased the speed and purity of dissection. Chromosomal deletions are often found in the vicinity of genes that protect cells from becoming cancerous. Using DNA prepared from 99 microdissected tumors, scientists in the UOB analyzed 45 genetic markers spanning a number of chromosomal regions that had been previously implicated in prostate carcinogenesis. The highest rate of deletion was observed on human chromosome 8, where the overall rate of loss was 86%. Approximately 80% of the cancers shared a common region of deletion within chromosome 8 (8p21). This region also overlaps a region recently identified as a locus for familial breast cancer. Human prostate cancer is thought to progress through a pre-malignant phase called prostatic intraepithelial neoplasia (PIN) prior to evolving into invasive cancer. In the region of chromosome 8 commonly deleted in cancer, deletions were also found in 63% of PIN lesions. This result suggests that abnormalities on 8p21 may be associated with early stages of prostate cancer development.