No evidence of germline PTEN mutations in familial prostate cancer

Forrest, Matthew S.

doi:10.1136/jmg.37.3.210

Cited by 13 publications

(7 citation statements)

References 19 publications

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“…Although to date a significant association has not been demonstrated between PTEN germline mutations and prostate cancer predisposition [18,19], data from studies of mice with heterozygous Pten deficiency (Ptenþ/À) and hypomorphic Pten (Pten hy/À) mutants, suggest PTEN as a potential prostate cancer…”

Section: Discussionmentioning

confidence: 99%

“…The contribution of PTEN germline mutations to Cowden Disease (MIM 158350) and the Bannayan-Ruvalcaba-Riley syndrome (MIM 153480), both characterized by an increased risk for multiple cancers [16,17], has raised the possibility that PTEN germline variants may also play a role in the pathogenesis of prostate cancer. However, to date, mutation analyses in HPC families did not support an association between PTEN germline mutations and prostate cancer risk [18,19], nor did linkage analysis support a prostate cancer predisposition gene in the PTEN region [19].…”

Section: Introductionmentioning

confidence: 99%

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Mutation screening and association study of the candidate prostate cancer susceptibility genesMSR1,PTEN, andKLF6

et al. 2006

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mutation screening and association study of the candidate prostate cancer susceptibility genesMSR1,PTEN, andKLF6

et al. 2006

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“…PTEN antagonizes the actions of PI3K by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3) and thereby exerts its tumor suppressor function mainly by restraining the PI3K/Akt prosurvival pathway (6). There is no evidence of germline PTEN mutations in hereditary prostate cancer (7,8), which suggests that interactions between PTEN haploinsufficiency and other genetic and/or epigenetic determinants are required for prostate tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

Akt-mediated phosphorylation of Bmi1 modulates its oncogenic potential, E3 ligase activity, and DNA damage repair activity in mouse prostate cancer

Nacerddine¹,

Beaudry²,

Ginjala³

et al. 2012

J. Clin. Invest.

108

105

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Prostate cancer (PCa) is a major lethal malignancy in men, but the molecular events and their interplay underlying prostate carcinogenesis remain poorly understood. Epigenetic events and the upregulation of polycomb group silencing proteins including Bmi1 have been described to occur during PCa progression. Here, we found that conditional overexpression of Bmi1 in mice induced prostatic intraepithelial neoplasia, and elicited invasive adenocarcinoma when combined with PTEN haploinsufficiency. In addition, Bmi1 and the PI3K/Akt pathway were coactivated in a substantial fraction of human high-grade tumors. We found that Akt mediated Bmi1 phosphorylation, enhancing its oncogenic potential in an Ink4a/Arf-independent manner. This process also modulated the DNA damage response and affected genomic stability. Together, our findings demonstrate the etiological role of Bmi1 in PCa, unravel an oncogenic collaboration between Bmi1 and the PI3K/Akt pathway, and provide mechanistic insights into the modulation of Bmi1 function by phosphorylation during prostate carcinogenesis.

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“…No deleterious variants were found to contribute to PCa susceptibility, which was consistent with previous studies. 13,14 Co-segregation of 10 rare variants, which were believed to give rise to high-penetrant HPC, was further evaluated by testing two microsatellite markers flanking PTEN in the HPC families. However, co-segregation was not observed in the HPC families.…”

Section: Discussionmentioning

confidence: 99%

Germ-line sequence variants of PTEN do not have an important role in hereditary and non-hereditary prostate cancer susceptibility

Xie

Sun

et al. 2011

J Hum Genet

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PTEN (phosphatase and tensin homolog deleted on chromosome 10) functions as a major tumor suppressor gene and is frequently deleted in different types of tumors including prostate cancer (PCa). It was hypothesized that germ-line genetic changes of PTEN affect susceptibility to PCa. Both common (with a minor allele frequency ≥5%) and rare (with a minor allele frequency <5%) germ-line variants of PTEN were comprehensively evaluated. A total of 15 germ-line variants were identified by re-sequencing the PTEN gene, including 5′ untranslated region, all nine exons, exon-intron junctions and 3′ untranslated region, in 188 probands of hereditary prostate cancer (HPC) families recruited from Johns Hopkins Hospital. Two microsatellite markers surrounding PTEN were used to test the co-segregation of 10 rare variants, which may give rise to highly penetrant in HPC. Two common single nucleotide polymorphisms (SNPs) were evaluated in the 188 HPC families using a family-based association study approach. To study low penetrant SNPs in PCa susceptibility, 33 SNPs covering PTEN were selected from the whole genome-wide association studies (GWAS) from our available case-control studies in Sweden (Cancer of the Prostate in Sweden (CAPS)) and the publicly available cancer genetic markers of susceptibility (CGEMS) study. Germ-line copy-number variations (CNVs) in PTEN were assessed in CAPS. Co-segregation of germ-line variants and PCa was not observed among HPC families and no significant differences in the allele frequencies were observed in sporadic cases and controls, aggressive and non-aggressive PCa (P >0.05). These results suggest that germ-line variants in PTEN do not have an important role in PCa susceptibility.

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No evidence of germline PTEN mutations in familial prostate cancer

Cited by 13 publications

References 19 publications

Mutation screening and association study of the candidate prostate cancer susceptibility genesMSR1,PTEN, andKLF6

Mutation screening and association study of the candidate prostate cancer susceptibility genesMSR1,PTEN, andKLF6

Akt-mediated phosphorylation of Bmi1 modulates its oncogenic potential, E3 ligase activity, and DNA damage repair activity in mouse prostate cancer

Germ-line sequence variants of PTEN do not have an important role in hereditary and non-hereditary prostate cancer susceptibility

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