title: Evaluation of PPP2R2A as a prostate cancer susceptibility gene: a comprehensive germline and somatic study.
abstract: 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.
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cheng
authors.forename: Wennuan
authors.initials: W
authors.lastname: Liu
authors.forename: Seong-Tae
authors.initials: ST
authors.lastname: Kim
authors.forename: Jishan
authors.initials: J
authors.lastname: Sun
authors.forename: Lingyi
authors.initials: L
authors.lastname: Lu
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.forename: Siqun Lilly
authors.initials: SL
authors.lastname: Zheng
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000483:Alleles; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D005091:Exons; D017353:Gene Deletion; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D054648:Protein Phosphatase 2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D004273:DNA, Neoplasm; C512974:PPP2R2A protein, human; D054648:Protein Phosphatase 2