SPOP Mutations in Prostate Cancer across Demographically Diverse Patient Cohorts
SPOP Mutations in Prostate Cancer across Demographically Diverse Patient Cohorts
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DOI：
10.1593/neo.131704
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发表时间：
2014-01-01
期刊：
影响因子：
4.8
通讯作者：
Rubin, Mark A.
中科院分区：
文献类型：
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作者：
Blattner, Mirjam;Lee, Daniel J.;Rubin, Mark A.
背景：斑点型POZ蛋白（SPOP）基因的复发性突变发生在高达15%的前列腺癌中。然而，不同人群中具有这些突变的癌症的频率和特征尚不清楚。目的：研究不同队列的SPOP突变，并验证采用高分辨率熔解（HRM）分析和桑格测序对福尔马林固定石蜡包埋材料进行突变分析的一系列试验。设计、设置和参与者：对来自6个国际队列的720例前列腺癌样本进行SPOP突变状态筛查，这些队列包括白人、非洲裔美国人和亚洲患者，包括前列腺特异性抗原筛查和未筛查人群。SPOP的状态与分子特征（ERG重排、PTEN缺失和CHD1缺失）以及临床和病理特征相关。结果和局限性：SPOP突变的总体频率为8.1%（4.6%至14.4%），SPOP突变与ERG重排呈负相关（P < .01），SPOP突变（SPOPmut）癌症的CHD1缺失率较高（P < .01）。SPOPmut癌的生化复发没有显著差异。这项研究的局限性包括由于样本质量和缺乏确定临床结果差异的能力而缺失突变数据。结论：在不同种族和人口统计学背景的前列腺癌患者中，SPOP突变率为4.6%至14.4%。SPOP突变与种族、临床或病理参数之间无显著相关性。SPOP突变与ERG重排的互斥性以及与CHD1缺失的高度相关性加强了SPOP突变作为前列腺癌的独特分子亚类的定义。
BACKGROUND: Recurrent mutations in the Speckle-Type POZ Protein (SPOP) gene occur in up to 15% of prostate cancers. However, the frequency and features of cancers with these mutations across different populations is unknown. OBJECTIVE: To investigate SPOP mutations across diverse cohorts and validate a series of assays employing high-resolution melting (HRM) analysis and Sanger sequencing for mutational analysis of formalin-fixed paraffin-embedded material. DESIGN, SETTING, AND PARTICIPANTS: 720 prostate cancer samples from six international cohorts spanning Caucasian, African American, and Asian patients, including both prostate-specific antigen-screened and unscreened populations, were screened for their SPOP mutation status. Status of SPOP was correlated to molecular features (ERG rearrangement, PTEN deletion, and CHD1 deletion) as well as clinical and pathologic features. RESULTS AND LIMITATIONS: Overall frequency of SPOP mutations was 8.1% (4.6% to 14.4%), SPOP mutation was inversely associated with ERG rearrangement (P < .01), and SPOP mutant (SPOPmut) cancers had higher rates of CHD1 deletions (P < .01). There were no significant differences in biochemical recurrence in SPOPmut cancers. Limitations of this study include missing mutational data due to sample quality and lack of power to identify a difference in clinical outcomes. CONCLUSION: SPOP is mutated in 4.6% to 14.4% of patients with prostate cancer across different ethnic and demographic backgrounds. There was no significant association between SPOP mutations with ethnicity, clinical, or pathologic parameters. Mutual exclusivity of SPOP mutation with ERG rearrangement as well as a high association with CHD1 deletion reinforces SPOP mutation as defining a distinct molecular subclass of prostate cancer.