Identification of Genomic Changes Mediating Melanoma Dev

介导黑色素瘤发展的基因组变化的鉴定

• 批准号: 6681466
• 负责人: JEFFREY M. TRENT
• 金额: --
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 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/6681466
• 关键词: carcinogenesis; chromosome aberrations; comparative genomic hybridization; complementary DNA; cytogenetics; differential display technique; family genetics; gene rearrangement; genetic susceptibility; genome; human genetic material tag; melanoma; microarray technology; molecular cloning; molecular genetics; molecular oncology; neoplasm /cancer genetics; neoplastic process; nucleic acid hybridization; subtraction hybridization; suppressor mutations

The purpose of this project is to determine the molecular basis underlying the genesis and progression of human malignant melanoma, and to identify novel genes associated with melanoma susceptibility in hereditary families. This project continues to have as its focus four component parts. 1) Molecular analysis of tumor progression [focuses on clonal progression identified by tissue array technology, CGH, and on clonal karyotypic alterations in malignant melanoma]; 2) Identification of genes differentially expressed during growth, differentiation and progression [focuses on suppression of tumorigenicity of melanoma, cDNA subtraction/differential display, retroviral-mediated reversion of tumor suppression, and DNA microarray analysis of differential gene expression]; 3) Genomic analysis of chromosome alterations [involves cloning of chromosomal breakpoints in melanoma, using microdissection and other molecular biology approaches]; 4) Analysis of susceptibility loci in hereditary melanoma families using linkage analysis [involves genotyping of families with non-p16 melanoma to identify loci, and ultimately cloning the genes conferring susceptibility to hereditary melanoma (cutaneous and ocular)]. In regards to part 1, a significant focus on WNT5A related to melanoma biology has been incorporated into our study and offers promising results.

该项目的目的是确定人类恶性黑色素瘤发生和发展的分子基础，并在遗传家族中确定与黑色素瘤易感性相关的新基因。该项目继续以四个组成部分为重点。1)肿瘤进展的分子分析[重点关注组织阵列技术、CGH鉴定的克隆进展，以及恶性黑色素瘤的克隆核型改变]；2)生长、分化和进展过程中差异表达基因的鉴定[重点研究黑色素瘤的致瘤性抑制、cDNA减法/差异显示、逆转录病毒介导的肿瘤抑制逆转、差异基因表达的DNA微阵列分析]；3)染色体改变的基因组分析[涉及黑色素瘤染色体断点的克隆，使用显微解剖和其他分子生物学方法]；4)使用连锁分析分析遗传性黑色素瘤家族的易感位点[涉及对非p16黑色素瘤家族进行基因分型以确定位点，并最终克隆遗传性黑色素瘤（皮肤和眼部）易感基因]。关于第1部分，我们将重点关注与黑色素瘤生物学相关的WNT5A纳入了我们的研究，并提供了有希望的结果。