Molecular Genetics of Prostate Cancer

前列腺癌的分子遗传学

• 批准号: 7068924
• 负责人: William Marston Linehan
• 金额: --
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7068924
• 关键词: cell line; cellular oncology; chromosome deletion; clinical research; gene expression; genetic library; genetic mapping; genetic markers; human genetic material tag; human subject; laser capture microdissection; male; molecular oncology; neoplasm /cancer genetics; neoplastic growth; neoplastic process; prostate neoplasms; prostate surgery; proteomics

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.

为了研究与前列腺癌的发生和发展相关的遗传事件，来自NCI泌尿肿瘤学分支（UOB）和病理学实验室（LOP）的科学家们利用了许多创新方法，这些方法围绕从异质组织中获取高度纯化的前列腺癌细胞。新的显微切割技术，允许这样的采购中开发的LOP;最新的这种技术，涉及激光捕获的细胞大大提高了速度和纯度的解剖。 染色体缺失通常发生在保护细胞免于癌变的基因附近。利用从99个显微切割的肿瘤中制备的DNA，UOB的科学家分析了45个遗传标记，这些标记跨越了先前与前列腺癌发生有关的许多染色体区域。在人类8号染色体上观察到最高的缺失率，其中总丢失率为86%。大约80%的癌症在8号染色体（8 p21）内共享一个共同的缺失区域。该区域也与最近被鉴定为家族性乳腺癌位点的区域重叠。 人类前列腺癌被认为在演变成浸润性癌症之前通过称为前列腺上皮内瘤变（PIN）的恶性前阶段进展。在癌症中通常缺失的8号染色体区域，在63%的PIN病变中也发现了缺失。这一结果表明，8 p21的异常可能与前列腺癌发展的早期阶段有关。