Evaluation of PPP2R2A as a prostate cancer susceptibility gene: a comprehensive germline and somatic study.
Evaluation of PPP2R2A as a prostate cancer susceptibility gene: a comprehensive germline and somatic study.
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DOI：
10.1016/j.cancergen.2011.05.002
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发表时间：
2011-07
期刊：
影响因子：
1.9
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Cheng Y;Liu W;Kim ST;Sun J;Lu L;Sun J;Zheng SL;Isaacs WB;Xu J
PPP 2 R2 A定位于8p21.2，编码蛋白磷酸酶2（PP 2A）的调节性B55亚家族的α亚型。PP 2A是四种主要的Ser/Thr磷酸酶之一，并且涉及细胞生长和分裂的负控制。由于其已知的功能和染色体区域内的位置，其中发现的证据连锁和体细胞杂合性丢失，我们假设，无论是体细胞拷贝数的变化或生殖系序列变异PPP 2 R2 A可能会增加前列腺癌（PCa）的风险。我们使用Affyssin SNP阵列检查了141个PCa样本中PPP 2 R2 A的缺失状态。发现PPP 2 R2 A在肿瘤样品中普遍缺失（67.1%），包括3个肿瘤中的纯合缺失（2.1%）。我们在96个遗传性前列腺癌（HPC）家族的先证者中进行PPP 2 R2 A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PPP 2 R2 A的10个SNP。PCa病例组与对照组、PCa侵袭性病例组与非侵袭性病例组的等位基因和基因型频率无显著性差异。两者合计，这些结果表明，体细胞缺失，而不是种系序列的PPP 2 R2 A变异可能发挥更重要的作用，前列腺癌的易感性。
PPP2R2A, mapped to 8p21.2, encodes for the α isoform of the regulatory B55 subfamily of the protein phosphatase 2 (PP2A). PP2A is one of the four major Ser/Thr 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 3 tumors (2.1%). We performed a mutation screen for PPP2R2A in 96 probands of hereditary prostate cancer (HPC) families. No high risk mutations were identified. Additionally, we reanalyzed 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.
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