Identification of Genomic Changes Mediating Melanoma Dev

该项目的目的是确定人类恶性黑色素瘤发生和进展的分子基础，并鉴定与遗传家族中黑色素瘤易感性相关的新基因。该项目仍然以四个组成部分为重点。 1）肿瘤进展的分子分析[重点是通过组织阵列技术、CGH识别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[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的易感性位点进行分析[涉及非 p16 黑色素瘤家族的基因分型以识别位点，并最终克隆赋予遗传性黑色素瘤（皮肤和眼部）易感性的基因]。关于第 1 部分，我们的研究重点关注与黑色素瘤生物学相关的 WNT5A，并提供了有希望的结果。

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.