Evaluation of PPP2R2A as a prostate cancer susceptibility gene: a comprehensive germline and somatic study

doi:10.1016/j.cancergen.2011.05.002

Cancer Genetics

Volume 204, Issue 7, July 2011, Pages 375-381

https://doi.org/10.1016/j.cancergen.2011.05.002 Get rights and content

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.

Section snippets

Subjects

The clinical samples used in somatic deletion analysis include a total of 141 PCa patients. All of the primary tumors were from PCa patients undergoing radical prostatectomy (RP) for treatment of clinically localized disease at JHH. For the analysis of somatic DNA copy number alterations in these tumors, we selected cases from which genomic DNA of sufficient quantity (>5 μg) and purity (>70% cancer cells for cancer specimens and no detectable cancer cells for normal samples) could be obtained

Detection of somatic PPP2R2A deletion in PCa

The deletion status of PPP2R2A in 141 pairs of samples was analyzed using our Affymetrix 500k/6.0 SNP array data. With the application of an allele-specific analysis algorithm, which takes advantage of genotype information and allele-specific intensities from paired samples to estimate DNA copy number, we found a total of 87 tumors (61.7%) showing a PPP2R2A gene deletion, including 3 (2.1%) homozygous deletions and 84 (59.6%) hemizygous deletions, among 141 prostate tumor samples. The

Discussion

This is the first report in which comprehensive somatic and germline analyses for PPP2R2A, a gene that is a potential tumor suppressor gene, were systemically evaluated in 141 clinical PCa samples, 96 HPC probands, as well as 983 aggressive cases and 572 controls from the JHH study. Interestingly, PPP2R2A was commonly deleted (61.7%) among prostate tumors with 2.1% having homozygous deletions. Again, multiple common and rare germline variants in PPP2R2A were identified, but the variants we

Acknowledgments

The authors thank all the study subjects who participated in this study. The authors thank Ms. T.S. Adams for editorial assistance. This study was supported by National Cancer Institute CA95052 to J.X.

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Original articleEvaluation of PPP2R2A as a prostate cancer susceptibility gene: a comprehensive germline and somatic study

Section snippets

Subjects

Detection of somatic PPP2R2A deletion in PCa

Discussion

Acknowledgments

Am J Hum Genet

Am J Hum Genet

Curr Opin Genet Dev

Neoplasia

Cell

J Biol Chem

Cancer statistics, 2010

CA Cancer J Clin

The complex genetic epidemiology of prostate cancer

Human Mol Genet

Where are the prostate cancer genes?–A summary of eight genome wide searches

Prostate

Linkage analysis of prostate cancer susceptibility: confirmation of linkage at 8p22-23

Hum Genet

Genomic scan of 254 hereditary prostate cancer families

Prostate

Genomewide linkage analysis of familial prostate cancer in the Japanese population

J Hum Genet

A genomewide linkage analysis for prostate cancer susceptibility genes in families from Germany

Eur J Hum Genet

Tumor suppressor genes in prostate cancer

Integration of somatic deletion analysis of prostate cancers and germline linkage analysis of prostate cancer families reveals two small consensus regions for prostate cancer genes at 8p

Cancer Res

Original article
Evaluation of PPP2R2A as a prostate cancer susceptibility gene: a comprehensive germline and somatic study