IDENTIFICATION OF GENOMIC CHANGES MEDIATING MELANOMA DEVELOPMENT AND PROGRESSION

这个项目的目的有两个：第一，确定人类恶性黑色素瘤发生和发展的分子基础。第二，在遗传家族中确定与黑色素瘤易感性相关的新基因。黑色素瘤是西方世界发病率增长最快的癌症，人们对这种重要疾病背后的分子遗传变化知之甚少。本项目可分为四个组成部分。1)肿瘤进展的分子分析。[本研究的重点是通过组织阵列技术（CGH）鉴定的克隆进展，以及恶性黑色素瘤的克隆核型改变]。2)生长、分化和进展过程中差异表达基因的鉴定。[这主要集中在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，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。这包括利用显微解剖和其他分子生物学方法克隆黑色素瘤的染色体断点。4)利用连锁分析分析遗传性黑色素瘤家族的易感位点{这涉及对非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易感基因。-癌症研究，基因定位，基因定位（人类），基因定位（非人类），遗传学，人类基因组研究，-人类受试者

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