IDENTIFICATION OF GENOMIC CHANGES MEDIATING MELANOMA DEVELOPMENT AND PROGRESSION

该项目的目的仍然是确定 染色体重排的分子基础， 人类恶性黑色素瘤的进展。黑色素瘤增长最快 2000年任何癌症（仅次于妇女肺癌）的发病率 在西方世界，人们对这种分子的了解非常少， 这种重要疾病背后的遗传变化。本工程选址 分为三个组成部分。1)肿瘤的分子分析 进展[This侧重于通过组织鉴定的克隆进展 解剖和比较基因组杂交，以及克隆 恶性黑色素瘤中的核型改变]。2)基因的鉴定 在生长、分化和进展期间差异表达。 [This重点是抑制6号染色体的致瘤性，cDNA 减影/差异显示，逆转录病毒介导的肿瘤逆转 差异基因抑制及基因芯片分析 表达式]。3)6号染色体变异的基因组分析。【这 涉及基于显微切割的染色体断裂点克隆， 黑色素瘤和其它恶性肿瘤]。

The purpose of this project continues to be the determination of the molecular basis of chromosome rearrangements underlying the genesis and progression of human malignant melanoma. Melanoma has the fastest growing rate of incidence of any cancer (next to lung cancer in women) in the Western world, and extraordinarily little is known about the molecular genetic changes underlying this important disease. This project can be divided into three component parts. 1) Molecular analysis of tumor progression. [This focuses on clonal progression identified by tissue dissection and comparative genomic hybridization, 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 chromosome 6, cDNA subtraction/differential display, retroviral-mediated reversion of tumor suppression, and DNA microarray analysis of differential gene expression]. 3) Genomic analysis of chromosome 6 alterations. [This involves microdissection-based cloning of chromosomal breakpoints in melanoma, and other malignancies].