Identification of a Melonoma Susceptibilty Gene at 1p22

1p22 处黑色素瘤易感基因的鉴定

• 批准号: 6891385
• 负责人: KEVIN M BROWN
• 金额: $ 3.53万
• 依托单位: TRANSLATIONAL GENOMICS RESEARCH INST
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-22 至 2006-01-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6891385
• 关键词: bioinformatics; cancer risk; cell line; chromosomes; comparative genomic hybridization; fibroblasts; gene mutation; genetic screening; genetic susceptibility; genotype; high throughput technology; human tissue; keratinocyte; linkage disequilibriums; melanocyte; melanoma; microarray technology; neoplasm /cancer genetics; nucleic acid sequence; oligonucleotides; postdoctoral investigator; single nucleotide polymorphism

DESCRIPTION (provided by applicant): Cutaneous malignant melanoma (CMM) incidence is rising, accounting for approximately 4% of cancer diagnoses in U.S. Recently, a novel CMM susceptibility locus was identified on chromosome 1 (1p22). To identify this gene Aim 1, we will use a multidisciplinary approach to comprehensively identify, prioritize, and screen genes within the critical region. We will construct a custom oligonucleotide microarray with probes representing all evolutionarily conserved sequence at 1p22 and assay expression in melanocytes and melanoma cell lines to identify all expressed genes in the region. We will use these arrays for CGH to screen for deletions in familial CMM patients and sporadic melanoma cell lines. We will SNP-genotype our families and perform a linkage disequilibrium based association study to narrow the 1p22 critical region. Based on these experiments, we will prioritize 1p22 candidates for high-throughput mutation screening. Once the CMM susceptibility gene is identified, we will look for genotype-genotype correlation, testing the hypothesis that Iow-penetrance genetic CMM risk factors act as modifiers to the penetrance of 1p22 mutations (Aim 2). Finally, we will determine the prevalence of 1p22 mutations in sporadic melanoma cell lines and tumors (Aim 3).

描述（由申请人提供）：皮肤恶性黑色素瘤（CMM）的发病率正在上升，约占美国癌症诊断的4%。最近，在1号染色体（1 p22）上鉴定出一种新的CMM易感基因座。为了鉴定这个基因Aim 1，我们将使用多学科方法来全面鉴定，优先考虑和筛选关键区域内的基因。我们将构建一个定制的寡核苷酸微阵列与探针代表所有进化保守序列在1 p22和黑素细胞和黑色素瘤细胞系中的表达，以确定所有表达的基因在该地区。我们将使用这些阵列的CGH筛查家族性CMM患者和散发性黑色素瘤细胞系的缺失。我们将对我们的家族进行SNP基因分型，并进行基于连锁不平衡的关联研究，以缩小1 p22关键区域。基于这些实验，我们将优先选择1 p22候选基因进行高通量突变筛选。一旦确定了CMM易感基因，我们将寻找基因型-基因型相关性，检验低突变率遗传性CMM风险因素作为1 p22突变突变率修饰因子的假设（目的2）。最后，我们将确定散发性黑色素瘤细胞系和肿瘤中1 p22突变的患病率（目的3）。