人类前列腺癌的综合基因组分析。
Integrative genomic profiling of human prostate cancer.
机构信息
Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
出版信息
Cancer Cell. 2010 Jul 13;18(1):11-22. doi: 10.1016/j.ccr.2010.05.026. Epub 2010 Jun 24.
Abstract
Annotation of prostate cancer genomes provides a foundation for discoveries that can impact disease understanding and treatment. Concordant assessment of DNA copy number, mRNA expression, and focused exon resequencing in 218 prostate cancer tumors identified the nuclear receptor coactivator NCOA2 as an oncogene in approximately 11% of tumors. Additionally, the androgen-driven TMPRSS2-ERG fusion was associated with a previously unrecognized, prostate-specific deletion at chromosome 3p14 that implicates FOXP1, RYBP, and SHQ1 as potential cooperative tumor suppressors. DNA copy-number data from primary tumors revealed that copy-number alterations robustly define clusters of low- and high-risk disease beyond that achieved by Gleason score. The genomic and clinical outcome data from these patients are now made available as a public resource.
摘要
前列腺癌基因组注释为疾病理解和治疗带来了重要发现。对 218 例前列腺癌肿瘤的 DNA 拷贝数、mRNA 表达和靶向外显子重测序进行一致性评估，发现核受体共激活因子 NCOA2 是约 11%肿瘤中的致癌基因。此外，雄激素驱动的 TMPRSS2-ERG 融合与以前未被识别的染色体 3p14 上的前列腺特异性缺失有关，这提示 FOXP1、RYBP 和 SHQ1 可能是潜在的协同肿瘤抑制因子。来自原发性肿瘤的 DNA 拷贝数数据显示，拷贝数改变在格里森评分的基础上更有力地定义了低风险和高风险疾病的聚类。这些患者的基因组和临床结局数据现已作为公共资源提供。
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