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发生和进展相关的遗传事件，NCI 泌尿肿瘤科 (UOB) 和病理学实验室 (LOP) 的科学家利用了许多围绕采购的创新方法。来自异质组织的高度纯化的前列腺癌细胞。 LOP 开发了允许此类采购的新型显微切割技术；最近的此类技术涉及激光捕获细胞，大大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于癌变的基因附近。 UOB 的科学家利用从 99 个显微解剖肿瘤中制备的 DNA，分析了跨越多个染色体区域的 45 个遗传标记，这些区域先前与前列腺癌发生有关。人类8号染色体的缺失率最高，总体缺失率为86%。大约 80% 的癌症在 8 号染色体 (8p21) 内有一个共同的缺失区域。该区域还与最近被确定为家族性乳腺癌位点的区域重叠。 人们认为，人类前列腺癌在演变成浸润性癌症之前，会经历一个称为前列腺上皮内瘤变 (PIN) 的癌前阶段。在癌症中常见缺失的 8 号染色体区域中，63% 的 PIN 病变中也发现了缺失。这一结果表明 8p21 的异常可能与前列腺癌发展的早期阶段有关。