Prostate Cancer Genome Sequencing Project

Prostate cancer is a prevalent cause of cancer morbidity and mortality in men. In order to characterize the full range of somatic mutations in protein-coding genes that may drive the growth of prostate cancer, we sequenced the exonic regions of genomic and tumor DNA from over 100 patients with high-risk primary prostate cancer. Using hybrid capture and paired end DNA sequencing, we identified mutations in several novel putative prostate cancer genes. We interrogated copy number changes across tumor genomes using high-density SNP arrays, and identified a molecular subtype of cancer characterized by mutation of the ubiquitin ligase subunit SPOP and copy number loss at specific genomic loci. ]]>
Primary prostate tumors from patients undergoing surgery for localized prostate cancer were selected based on high density of tumor tissue. DNA was extracted from prostate tumor tissue and from either adjacent normal prostate or blood for use as a normal DNA comparator. DNA was assessed for high quality and integrity on Affymetrix SNP 6.0 arrays and by agarose gel electrophoresis. ]]>

前列腺癌是引发男性癌症发病与死亡的常见病因。为全面刻画可能驱动前列腺癌发生发展的蛋白编码基因体细胞突变全景，我们对100余例高危原发性前列腺癌患者的基因组DNA与肿瘤DNA的外显子区域开展了测序。通过杂交捕获联合双端DNA测序技术，我们在多个潜在新型前列腺癌致病相关基因中鉴定出突变位点。我们采用高密度SNP（Single Nucleotide Polymorphism，单核苷酸多态性）阵列分析肿瘤全基因组的拷贝数变异，并鉴定出一种以泛素连接酶亚基SPOP突变及特定基因组位点拷贝数缺失为特征的癌症分子亚型。
本研究选取因局限性前列腺癌接受手术治疗的患者的原发性前列腺肿瘤组织，筛选标准为肿瘤组织占比充足。从前列腺肿瘤组织以及配对的癌旁正常前列腺组织或外周血中提取DNA，作为正常DNA对照样本。通过Affymetrix SNP 6.0阵列与琼脂糖凝胶电泳检测DNA的质量与完整性。