Review of allelic loss and gain in prostate cancer

Abstract

There are three nearly ubiquitous genomic "imbalances" in prostate cancer cells: 1) loss of sequences from the short arm of chromosomes 8, 2) loss of sequences from the long arm of chromosome 13q, and 3) gain of sequences on the long arm of chromosome 8, particularly in advanced disease. Candidate tumor suppressor genes and oncogenes affected by this trio of consistent changes include the c-myc gene on chromosome 8q24, the RB gene at 13q14, and potentially multiple novel genes on the short arm of chromosome 8, with a gene located more proximally potentially involved in tumor initiation and a gene or genes located more distally involved in tumor progression. Loss of regions of chromosomes 2q, 5q, 6q, 7p and 7q, 9p, 10p and 10q, 16q, 17p and 17q, and 18q, and gain of regions of 1q, 2p, 3p and 3q, 7p and 7q, 11p, 17q, and Xq have also been detected in the range of 25-50% of tumors studied. Analysis of candidate tumor suppressor genes in these regions is still in its early stages. Similarly, potential oncogenes on a series of chromosomal arms which undergo frequent amplification remain essentially uncharacterized. The basic outline of the chromosomal aberrations in prostate cancer has been well established; the details of the story remain to be filled in. This paper reviews the advantages and disadvantages of various techniques for detection of genomic loss and gain in prostate cancer cells, and reviews published reports of loss and gain in prostate cancer, focusing primarily on reports using microsatellite analysis, Southern analysis, and comparative genomic hybridization. Fluorescence in situ hybridization (FISH) based analyses of selected regions are also reviewed.

Chromosomal changes during development and progression of prostate adenocarcinomas

“…The frequent finding of gain on chromosome 12q is in good agreement with a recent publication (Sattler et al, 1999) reporting on frequent copy number gains in human prostate cancer. Losses on 8p and 6q as well as gains on 8q and of chromosome 7, which were considered to be typical aberrations for prostate cancer (for review see Bova and Isaacs, 1996), were also detected in primary tumours investigated in this study, but at a lower frequency. This fact can be partly explained by the smaller number of cases in our study compared to the literature data.…”

“…Application of CGH and fluorescence in situ hybridization (FISH) to primary tumours of prostatic adenocarcinomas revealed consistent changes on chromosomes 7, 8p, 10, 13q, 16, 17 and 18q (Brothman et al, 1994;Macoska et al, 1994;Matsuyama et al, 1994;Joos et al, 1995;Qian et al, 1995;Visakorpi et al, 1995;Bova and Isaacs, 1996;Cher et al, 1996;Huang et al, 1996;Deubler et al, 1997). However, cytogenetic changes in prostatic intraepithelial neoplasias (PIN) which are considered as premalignant lesions and which are often present besides the invasive tumour are only poorly characterized cytogenetically (Alers et al, 1995;Qian et al, 1995;Zitzelsberger et al, 1998).…”

Loss of p53 and c-myc Overrepresentation in Stage T2-3N1-3M0 Prostate Cancer are Potential Markers for Cancer Progression

“…Molecular genetic studies have identified multiple genetic changes in prostate cancers (5,6). These include loss or gain of specific regions or whole chromosomes, gene amplification, and structural alterations that lead to overexpression or activation of oncogenes or inactivation of putative tumor suppressor genes (5,6).…”

“…These include loss or gain of specific regions or whole chromosomes, gene amplification, and structural alterations that lead to overexpression or activation of oncogenes or inactivation of putative tumor suppressor genes (5,6). For example, frequent allelic loss of the LPL gene (8p22) in prostate cancer suggests that a tumor suppressor gene (or genes) is located in this region (7)(8)(9)(10)(11).…”

Hormone-refractory prostate cancer: a multi-step and multi-event process

“…LOH involving specific chromosomes has been demonstrated in prostate carcinomas. 75 The most commonly observed LOH involved 16q and 10q, with 30% of the examined cases demonstrating losses. 76 Additional LOH loci in prostate cancer included 3p, 7q, 9q, 10p, 10q, 11p, 13q, 16p, 16q, 17p and 18q.…”