MOLECULAR PATHOGENESIS OF PARATHYROID NEOPLASIA

甲状旁腺肿瘤的分子发病机制

• 批准号: 2084408
• 负责人: VINCENT L. CRYNS
• 金额: $ 6.73万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2084408
• 关键词: adenoma; carcinoma; cell cycle proteins; complementary DNA; gene expression; gene rearrangement; genetic library; human subject; loss of heterozygosity; neoplasm /cancer genetics; neoplastic transformation; oncogenes; parathyroid hyperplasia; parathyroid neoplasms; restriction fragment length polymorphism; subtraction hybridization; tumor suppressor genes

Specifically, the long-term objective of the proposed research is to identify and characterize genes that are important in the pathogenesis of human parathyroid neoplasms (both adenomas and carcinomas). Although the majority of these genes have yet to be identified, genetic rearrangement and overexpression of a cell cycle regulator (PRAD1 or human cyclin D1) has been implicated in the pathogenesis of about 5% of parathyroid tumors. The underlying hypothesis for the proposed studies, then, is that abnormalities in other cell cycle regulators (p53, retinoblastoma (Rb) and cyclins other than PRAD1) and/or additional candidate oncogenes (some perhaps by their overexpression) are likely to be important in the pathogenesis of these tumors. To begin to test this hypothesis, human parathyroid adenomas will be examined for: (i) abnormalities in the p53 and Rb genes using "loss of heterozygosity" (LOH) studies and subsequent characterization of the remaining, non- deleted allele in tumors showing LOH; and (il) tumor-specific overexpression (or unique expression) of cDNAs isolated by subtractive hybridization, one or more of which may encode a putative oncogene or a gene functionally linked to an oncogene. These studies should provide important insights into the molecular mechanisms of tumorigenesis in these neoplasms, and could potentially have broader clinical and biological ramifications as has been the case for PRAD1).

具体而言，拟议的研究的长期目标是 识别和表征重要的基因 人甲状旁腺肿瘤的发病机理（腺瘤和 癌）。尽管这些基因的大多数尚未 鉴定出细胞的遗传重排和过表达 周期调节剂（PRAD1或人类细胞周期蛋白D1）已与 大约5％的甲状旁腺肿瘤的发病机理。基础 因此，拟议的研究的假设是异常 其他细胞周期调节剂（p53，视网膜细胞瘤（RB）和细胞周期蛋白 除了prad1）和/或其他候选癌症（有些 也许通过他们的过表达）在 这些肿瘤的发病机理。为了开始检验这一假设， 人类甲状旁腺腺瘤将进行检查：（i）异常 在p53和Rb基因中，使用“杂合性丧失”（LOH） 其余的，非 - 的研究和随后的表征 在显示LOH的肿瘤中删除了等位基因； （IL）肿瘤特异性 由CDNA的过表达（或独特的表达）通过 减法杂交，其中一个或多个可能编码A 推定的癌基因或与癌基因功能相关的基因。 这些研究应提供对分子的重要见解 在这些肿瘤中的肿瘤发生机制，可以 可能具有更广泛的临床和生物分析 Prad1是这种情况。