MOLECULAR PATHOGENESIS OF PARATHYROID NEOPLASIA

甲状旁腺肿瘤的分子发病机制

• 批准号: 2084409
• 负责人: VINCENT L. CRYNS
• 金额: $ 8.08万
• 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 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2084409
• 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).

具体来说，拟议研究的长期目标是 识别和表征重要的基因 人类甲状旁腺肿瘤（腺瘤和腺瘤）的发病机制 癌）。尽管这些基因中的大多数尚未被 细胞的鉴定、基因重排和过度表达 循环调节因子（PRAD1 或人细胞周期蛋白 D1）与 约5%的甲状旁腺肿瘤发病。底层的 那么，拟议研究的假设是，异常 其他细胞周期调节因子（p53、视网膜母细胞瘤 (Rb) 和细胞周期蛋白 除 PRAD1 之外）和/或其他候选癌基因（某些 也许通过他们的过度表达）可能在 这些肿瘤的发病机制。为了开始检验这个假设， 将检查人甲状旁腺腺瘤是否有： (i) 异常 在 p53 和 Rb 基因中使用“杂合性丢失”(LOH) 研究和随后对剩余的、非 显示 LOH 的肿瘤中删除的等位基因； (il) 肿瘤特异性 分离的 cDNA 的过表达（或独特表达） 消减杂交，其中一个或多个可以编码 假定的癌基因或与癌基因功能相关的基因。 这些研究应该为分子生物学提供重要的见解。 这些肿瘤的肿瘤发生机制，并且可以 可能具有更广泛的临床和生物学影响 PRAD1 就是这种情况）。