Allelic loss of chromosomes 16q and 10q in human prostate cancer.

Abstract

Recent advances in understanding the molecular genetics of common adult tumors have indicated that multiple genetic alterations including the activation of oncogenes and the inactivation of tumor suppressor genes are important in the pathogenesis of these tumors. Loss of heterozygosity is a hallmark of tumor suppressor gene inactivation and has been used to identify chromosomal regions that contain these genes. We have examined allelic loss in the most common tumor in men, prostate cancer. Twenty-eight prostate cancer specimens have been examined for loss of heterozygosity at 11 different chromosomal arms including 3p, 7q, 9q, lOp, lOq, Ulp, 13q, 16p, 16q, 17p, and 18q. Fifty-four percent'(13/24) of clinically localized tumors and 4 of 4 metastatic tumors showed loss of heterozygosity on at least one chromosome. Chromosomes 16q and lOq exhibited the highest frequency of loss of heterozygosity with 30% of tumors showing loss at these chromosomes. These data demonstrate that allelic loss is a common event in prostate cancer and suggest that chromosomes 16q and lOq may contain the sites of tumor suppressor genes important in the pathogenesis of human prostate cancer.

Molecular analysis of the FHIT gene in human prostate cancer

“…Little is known of the acquired genetic changes that drive these tumors through the various stages of carcinogenesis. The most consistent genetic alterations in adenocarcinoma of the prostate are loss of heterozygosity (LOH) involving chromosome arms 7q, 8p, 10q, 13q, 16q, 17q and 18q, pointing to the presence of tumor suppressor genes (TSGs) in these deleted regions and their involvement in prostate carcinogenesis (Zenklusen et al, 1994;Bova et al, 1993;Ittman, 1996;Cooney et al, 1996;Carter et al, 1990;Gao et al, 1995;Latil et al, 1994). The demonstration of LOH in certain chromosomes has potentially implicated previously identi®ed TSGs, incuding CDH1 on 16q (Umbas et al, 1992), and DCC on 18q (Gao et al, 1993), even though the precise role of these TSGs in prostate cancer is controversial.…”

Molecular biology of prostate cancer

“…In another study the most frequent locus (53%) altered by MSI was 10q23-24, 291 which is a common site of allelic loss in PC. 175 The frequency of MSI in latent cancer is lower than in clinical PC. 292 …”

“…There are frequent deletions in the region of chromosome 16q where the E-cadherin gene is located. 175,176 Loss of E-cadherin function has been implicated in the pathogenesis of sporadic colorectal and other cancers. 177 Patients with germline mutation in the Ecadherin gene face a 70-80% likelihood of developing familial gastric cancer during their lifetime.…”

Allelic imbalance and biochemical outcome after radical prostatectomy

“…[10][11][12][13][14][15][16][17][18][19][20][21][22][23] The sites most frequently lost in somatic cancers include 8p, 10q, 13q, 16q and 18q, [11][12][13]15,20,22,23 and losses on 1q are associated with hereditary prostate cancer. 19 Some losses, such as those on 8p and 13q, are associated with early prostate cancer.…”

“…19 Some losses, such as those on 8p and 13q, are associated with early prostate cancer. 11,12,22,23 Others, such as those on 11p and 16q, 15,[20][21][22]24 are more frequent in advanced disease. Several studies have reported an association of AI at certain loci with histopathological features of the RP specimen, including advanced stage, 13,[25][26][27] high Gleason grade 13,26 and perineural invasion.…”