Using array CGH to identify prostate cancer genes

描述（由申请人提供）：前列腺癌是大多数西方国家最常诊断的非皮肤癌。双胞胎和家族研究表明，家族史是前列腺癌的明确危险因素。 然而，尽管做出了重大努力和多重连锁研究，但只有少数遗传变化被确定为前列腺癌的易感性，这只能解释少数家族。鉴于遗传性前列腺癌的复杂性，需要与传统的连锁分析方法互补的新方法来协助前列腺癌的基因鉴定。 我们建议使用阵列为基础的比较基因组杂交（aCGH）在前列腺癌的遗传性家族，进一步识别基因的重要遗传性前列腺癌，与国际前列腺癌遗传学联盟的成员合作。在特定目标1中，我们将使用Acgh描述遗传性前列腺癌家族中前列腺癌的染色体扩增和缺失，并将研究结果与先前确定的连锁区域相关联。在具体目标2中，我们将确定是否有共同的染色体丢失或获得家庭成员之间共享的区域，这表明一个共享的遗传变化的位点。作为一个探索性的目标，我们将对aCGH数据进行聚类分析，以探索我们是否可以使用肿瘤特征区分家族，从而减少前列腺癌连锁研究中的遗传异质性。这些目标共同代表了在识别前列腺癌易感基因方面迈出的重要一步。此外，他们将提供重要的信息，体细胞染色体扩增和删除在前列腺癌的发展规模上以前无法实现。识别遗传性前列腺癌中的基因将为高风险病例和普通人群中与前列腺癌发展相关的遗传变异和生物学提供重要见解，进一步提高我们预测谁患前列腺癌风险最高的能力。

DESCRIPTION (provided by applicant): Prostate cancer is the most commonly diagnosed non-skin cancer in most western countries. Family history is well established as a clear risk factor for prostate cancer, as demonstrated by twin and familial studies. However, despite major efforts and multiple linkage studies, only a few genetic changes have been identified that confer susceptibility to prostate cancer, which explain only a minority of the families. Given the complexity of hereditary prostate cancer, novel approaches complementary to the traditional approach of linkage analysis, are needed to assist with gene identification in prostate cancer. We propose to use array based comparative genomic hybridization (aCGH) in prostate cancers from hereditary families to further the identification of genes important in hereditary prostate cancer, in collaboration with members of the International Consortium for Prostate Cancer Genetics. In Specific Aim 1, we will characterize the chromosomal amplifications and deletions in prostate cancers from hereditary prostate families using Acgh and correlate the findings with previously identified regions of linkage. In Specific Aim 2, we will determine if there are common regions of chromosomal loss or gain shared between family members suggesting the locus of a shared genetic change. As an exploratory aim, we will perform cluster analyses on the aCGH data to explore whether we can differentiate between families using tumor profiles, and thus decrease the genetic heterogeneity in prostate cancer linkage studies. Together these aims represent a significant step forward in the effort to identify prostate cancer susceptibility genes. In addition, they will provide important information about somatic chromosomal amplifications and deletions in prostate cancer development on a scale not previously achievable. Identifying genes in hereditary prostate cancer will provide important insights into genetic variation and biology associated with prostate cancer development both in high-risk cases and the general population, furthering our ability to predict who is at highest risk of prostate cancer.