IDENTIFICATION OF GENOMIC CHANGES MEDIATING MELANOMA DEVELOPMENT AND PROGRESSION

介导黑色素瘤发生和进展的基因组变化的鉴定

• 批准号: 6290280
• 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/6290280
• 关键词: carcinogenesis; chromosome aberrations; comparative genomic hybridization; complementary DNA; cytogenetics; gene rearrangement; genome; human genetic material tag; melanoma; molecular cloning; molecular genetics; molecular oncology; neoplasm /cancer genetics; neoplastic process; nucleic acid hybridization; suppressor mutations

The purpose of this project is twofold: first to determine the molecular basis underlying the genesis and progression of human malignant melanoma. The second, to identify novel genes associated with melanoma susceptibility in hereditary families. Melanoma has the fastest growing rate of incidence of any cancer in the Western world, and little is known about the molecular genetic changes underlying this important disease. This project can be divided into four component parts. 1) Molecular analysis of tumor progression. [This 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. [This 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. [This 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 {This involves genotyping of families with non-p16 melanoma to identify loci, and ultimately clone the genes conferring susceptibility to hereditary melanoma. - Cancer Research, Gene Mapping, gene mapping (HUMAN), Gene mapping (non-human), Genetics,Human Genome Research, - Human Subjects

该项目的目的有两个：首先确定人类恶性黑色素瘤发生和进展的分子基础。第二，确定遗传家族中与黑色素瘤易感性相关的新基因。黑色素瘤是西方世界所有癌症中发病率增长最快的，但人们对这种重要疾病背后的分子遗传变化知之甚少。该项目可分为四个组成部分。 1）肿瘤进展的分子分析。 [重点关注通过组织阵列技术、CGH 鉴定的克隆进展，以及恶性黑色素瘤的克隆核型改变]。 2) 鉴定生长、分化和进展过程中差异表达的基因。 [重点关注黑色素瘤致瘤性的抑制、cDNA 消减/差异显示、逆转录病毒介导的肿瘤抑制逆转以及差异基因表达的 DNA 微阵列分析]。 3）染色体改变的基因组分析。 [这涉及使用显微切割和其他分子生物学方法克隆黑色素瘤中的染色体断点]。 4) 使用连锁分析对遗传性黑色素瘤家族中的易感性位点进行分析{这涉及对非p16黑色素瘤家族进行基因分型以识别位点，并最终克隆赋予遗传性黑色素瘤易感性的基因。 - 癌症研究、基因图谱、基因图谱（人类）、基因图谱（非人类）、遗传学、人类基因组研究、- 人类受试者