In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 4854-4854
Abstract:
The PTEN (Phospatase and Tensin Homolog deleted on chromosome Ten) gene is frequently altered in prostate cancer. To determine the prevalence and clinical significance of different mechanisms of PTEN inactivation, we analyzed 4,699 hormone-naïve and 57 hormone-refractory prostate cancers by fluorescence in situ hybridization for PTEN deletion. In addition, PTEN mutations and promoter methylation were analyzed in subsets of 149 and 34 tumors. PTEN deletions were present in 20.2% (458/2,266) of prostate cancers harboring and heterozygous (8.1%) and homozygous (12.1%) deletions. Deletions of PTEN were linked to advanced tumor stage (p & lt;0.0001), high Gleason grade (p & lt;0.0001), presence of lymph-node metastasis (p=0.0002), hormone refractory disease (p & lt;0.0001), presence of ERG gene fusion (p & lt;0.0001), and nuclear p53 accumulation (p & lt;0.0001). PTEN deletions were also associated with early PSA recurrence in univariate (p & lt;0.0001) and multivariate analysis (p=0.0158) if compared to the established risk factors pT stage, Gleason grade, and preoperative PSA level. The PTEN deletion had the identical prognostic impact in both in ERG fusion-positive and -negative tumors. PTEN mutations were found in 4 of 26 (15%) of cancers with heterozygous PTEN deletion, but in only 1 of 59 (2%) of cancers without PTEN deletion (p=0.0183). Analysis of the PTEN promoter for methylation changes in 34 tumors revealed no aberrations. The results of this study demonstrate that biallelic inactivation of PTEN, either by homozygous deletion or by deletion of one allele and mutation of the second one, occurs in the majority of prostate cancers with PTEN alteration and is characteristic feature for a particularly aggressive subset of metastatic and hormone-refractory prostate cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4854. doi:1538-7445.AM2012-4854
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-4854
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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