Cheng Yu, Liu Wennuan, Kim Seong-Tae, Sun Jishan, Lu Lingyi, Sun Jielin, Zheng Siqun Lilly, Isaacs William B, Xu Jianfeng
Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Cancer Genet. 2011 Jul;204(7):375-81. doi: 10.1016/j.cancergen.2011.05.002.
PPP2R2A, mapped to 8p21.2, codes for the α isoform of the regulatory B55 subfamily of protein phosphatase 2 (PP2A). PP2A is one of the four major serine/threonine phosphatases and is implicated in the negative control of cell growth and division. Because of its known functions and location within a chromosomal region where evidence for linkage and somatic loss of heterozygosity was found, we hypothesized that either somatic copy number changes or germline sequence variants in PPP2R2A may increase prostate cancer (PCa) risk. We examined PPP2R2A deletion status in 141 PCa samples using Affymetrix SNP arrays. It was found that PPP2R2A was commonly (67.1%) deleted in tumor samples, including a homozygous deletion in three tumors (2.1%). We performed a mutation screen for PPP2R2A in 96 probands of hereditary prostate cancer families. No high risk mutations were identified. In addition, we re-analyzed 10 SNPs of PPP2R2A in sporadic PCa cases and controls. No significant differences in the allele and genotype frequencies were observed among either PCa cases and controls or PCa aggressive and non-aggressive cases. Taken together, these results suggest that a somatic deletion rather than germline sequence variants of PPP2R2A may play a more important role in PCa susceptibility.
PPP2R2A基因定位于8p21.2，编码蛋白磷酸酶2（PP2A）调节性B55亚家族的α异构体。PP2A是四种主要的丝氨酸/苏氨酸磷酸酶之一，参与细胞生长和分裂的负调控。鉴于其已知功能以及位于发现连锁和杂合性体细胞缺失证据的染色体区域内，我们推测PPP2R2A的体细胞拷贝数变化或种系序列变异可能会增加前列腺癌（PCa）风险。我们使用Affymetrix SNP阵列检测了141例PCa样本中PPP2R2A的缺失状态。结果发现，PPP2R2A在肿瘤样本中普遍缺失（67.1%），其中三例肿瘤（2.1%）存在纯合缺失。我们对96个遗传性前列腺癌家族的先证者进行了PPP2R2A的突变筛查。未发现高风险突变。此外，我们重新分析了散发性PCa病例和对照中PPP2R2A的10个单核苷酸多态性。在PCa病例与对照之间或PCa侵袭性与非侵袭性病例之间，等位基因和基因型频率均未观察到显著差异。综上所述，这些结果表明，PPP2R2A的体细胞缺失而非种系序列变异可能在PCa易感性中起更重要的作用。
