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，寻找与遗传性黑色素瘤易感性相关的新基因。在西方世界，黑色素瘤的发病率是所有癌症中增长最快的，人们对这种重要疾病背后的分子遗传变化知之甚少。这个项目可以分为四个组成部分。1)肿瘤进展的分子分析。[重点是通过组织阵列技术、CGH和恶性黑色素瘤的克隆性核型改变鉴定的克隆进展]。2)发现在生长、分化和发展过程中差异表达的基因。[重点是黑色素瘤的致瘤性抑制、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。[这涉及使用显微解剖和其他分子生物学方法克隆黑色素瘤的染色体断裂点]。4)利用连锁分析对遗传性黑色素瘤家系的易感基因进行分析{这包括对非p16黑色素瘤家系进行基因分型，以确定基因座，并最终克隆与遗传性黑色素瘤易感的基因。-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-人类科目

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