Genetic markers useful for distinguishing between organ‐confined and locally advanced prostate cancer

Abstract

Prostate cancer is one of the most commonly diagnosed cancers and the second leading cause of cancer deaths among men in the United States. In this study, we performed comparative genomic hybridization (CGH) on 45 primary prostate adenocarcinomas to determine genetic markers that could be useful for distinguishing between organ-confined and locally advanced prostate cancer. Of these tumors, 24 were pT2 stage, 21 were pT3b; 20 had low Gleason scores (GS), 25 had high GS. The most common chromosomal alterations in all 45 tumors included losses on 8p (57.8%), 10q21-->qter (40.0%), 16q (35.6%), 11q21-->qter (28.9%), 16p (22.2%), 6q22-->24 (22.2%), 10p (20.0%), 5q31-->qter (17.8%), 6p (17.8%), 15q22-->qter (15.6%), and 17p (15.6%) as well as gains on 7cen-->p14 (20.0%), 7cen-->q22 (20.0%), and Xcen-->q21 (17.8%). Contingency table analysis showed that losses of 8p, 10q25-->qter, 6p21, 6q24-->qter, and 15q22-->qter were significantly increased in frequency (P < 0.05) with increasing stage and/or GS. A model was created following multivariate logistic regression analysis that was predictive of tumor stage in approximately 90% of the tumors studied. This model suggests that loss of 8p is the most valuable predictor of stage. These findings suggest that chromosomal regions identified in this study may be useful for distinguishing between organ-confined and locally advanced prostate tumors.

Genome-wide analysis of allelic imbalance in prostate cancer using the Affymetrix 50K SNP mapping array

“…Previous reports have indicated that early-stage organ-confined prostate tumours did not display chromosome-level imbalances, and that balanced cytogenetic and epigenetic changes could be responsible for tumour development (Fu et al, 2000;Chu et al, 2003). A combination of microdissection of tumour tissue to maximise the yield of neoplastic tissue and a new high-resolution methodology enabled us to show that LOH and copy number loss have similar frequency in organ-confined and metastatic tumours, indicating that LOH is an early event in PCa tumour development.…”

Asynchronous Growth of Prostate Cancer Is Reflected by Circulating Tumor Cells Delivered from Distinct, Even Small Foci, Harboring Loss of Heterozygosity of the PTEN Gene

“…The marker D7S522 on 7q31.1 (11) is associated with tumor progression and is colocalized with caveolin-1. One of the most frequently deleted chromosomal regions in prostate carcinoma is localized at 8p21-22, and this deletion is assumed to be an early event in prostate cancer progression (12,13). The marker D10S541 is colocalized with the well-known tumor suppressor gene PTEN (13).…”

Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myeloma

“…The most common primary translocations are found in both the premalignant monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM), and in multiple myeloma itself, and involve the immunoglobulin heavy chain (IgH) gene at 14q32: t(4;14), t(6;14), t (11;14), t(14;16), and t (14;20). 1 Trisomies of chromosomes 3,5,7,9,11,15,19, and 21 plus gains of 1q are the most frequent gains along with deletions of 13q, 6q, 8p, 16q, and 17p. [2][3][4] It is difficult to determine the precise significance of large areas of gain or loss; therefore, we have previously used single-nucleotide polymorphism (SNP)-based arrays, 5 and others have used array-based comparative genomic hybridization (CGH), 6,7 to define with greater precision the size and location of regions of deletion or gain.…”

“…6 Deletions of all or part of 16q have also been described in a large number of nonhematologic cancers, including breast and prostate carcinomas and Wilms tumors. [11][12][13] Specifically, a WW domain-containing oxidoreductase gene (WWOX) has been identified at 16q23.1 at the common fragile site FRA16D as being the likely tumor suppressor gene deleted in this region. [14][15][16][17][18][19][20] The primary IgH translocation t(14;16) occurs at WWOX 21 and juxtaposes the oncogene MAF into the IgH locus, leading to MAF overexpression.…”