RESTRICTION FRAGMENT LENGTH POLYMORPHISMS IN NORMAL AND NEOPLASTIC TISSUES

正常和肿瘤组织中的限制性片段长度多态性

• 批准号: 6100918
• 负责人: B ZBAR
• 金额: --
• 依托单位: DIVISION OF BASIC 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/6100918
• 关键词: 3T3 cells; clinical research; family genetics; human genetic material tag; human subject; kidney neoplasms; neoplasm /cancer genetics; protein tyrosine kinase; protooncogene; restriction fragment length polymorphism; tissue /cell culture; transfection

The major goal of this research project is to identify and characterize genes involved in the pathogenesis of human kidney cancer. Our major accomplishments this year are: 1. We demonstrated that mutations in the MET proto- oncogene are responsible for a recently recognized inherited form of kidney cancer, hereditary papillary renal carcinoma (HPCR). In contrast to our previous studies with the von Hippel-Lindau disease gene, mutations in the MET proto-oncogene were all missense, and were located in the catalytic domain of the protein. Mutations in the MET proto-oncogene were detected in 6/7 HPRC families, and in a subset of sporadic papillary renal carcinomas. 2. We demonstrated that the mutations in MET produced a gain-of- function. The mutations in MET detected in patients with HPRC and sporadic tumors produced malignant transformation of NIH 3T3 cells. Constitutive phosphorylation of the MET protein was demonstrated in mouse cells transfected with mutant MET genes. 3. Some of the mutations detected in MET were located in residues homologous to those mutated in other receptor tyrosine kinases, RET and KIT. These results suggest that we have identified residues of the catalytic domain common to several receptor tyrosine kinases that in mutant form produce disease. 4. We have identified another distinct inherited form of renal neoplasia. So far, we have identified 5 families with multiple members affected with renal oncocytoma. Affected individuals have multiple, bilateral renal oncocytomas.

这个研究项目的主要目标是识别和表征