Three independently deleted regions at chromosome arm 16q in human prostate cancer: allelic loss at 16q24.1–q24.2 is associated with aggressive behaviour of the disease, recurrent growth, poor differentiation of the tumour and poor prognosis for the patient

Abstract

Prostate cancer is one of the most common cancers among men in many Western countries, including Finland. However, the molecular genetic events associated with the development and progression of the disease are poorly known. According to the multistep model of carcinogenesis, several genetic aberrations take place in prostate cancer, but only a few genes potentially involved in prostatic carcinogenesis have been identified.It has been suggested that genetic alterations take place in several chromosomal regions in prostate cancer and, in comparative genomic hybridization (CGH) studies, the long arm of chromosome 16 is among those showing the most frequent loss (Joos et al, 1995;Visakorpi et al, 1995;Cher et al, 1996). Losses at chromosome 16 have been reported to occur almost exclusively in the long arm (q) (Bergerheim et al, 1991;Visakorpi et al, 1995;Cher et al, 1996). Both primary and metastatic tumours have been found to show allelic loss at 16q, and the occurrence of loss of heterozygosity (LOH) has also been associated with clinicopathological variables such as aggressive and metastatic behaviour of the disease and poor differentiation of the tumour (Carter et al, 1990;Suzuki et al, 1996;Elo et al, 1997;Latil et al, 1997). The most common area of deletion has been suggested to be distal in 16q, but the most recent results have indicated evidence of loss of several independent regions in 16q (Suzuki et al, 1996;Elo et al, 1997;Latil et al, 1997).Particular interest in losses at 16q has been paid to the region 16q21.1, where a potential tumour-suppressor gene, that for Ecadherin, is located. Decreased E-cadherin expression has been associated with poor prognosis of prostate cancer (Umbas et al, 1994). Recently, the regions of loss at chromosome arm 16q have been narrowed down. It has been suggested in several reports that losses at 16q are concentrated in three independent regions (Suzuki et al, 1996;Latil et al, 1997). The proximal area of loss is suggested to be located somewhere at 16q21.1 and the distal area of loss has been suggested to lie at 16q24.3. The central region of loss has been reported to be at 16q23.2 (Latil et al, 1997), but it has also been reported to be located at 16q23.2-q24.1 (Suzuki et al, 1996). Our recent data indicate that a 7.6-cM central area of loss is located at 16q24.1-q24.2, between markers D16S504 and D16S422. In addition, LOH at 16q24.1-q24.2 (HSD17B2 and D16S422) was found to be the most frequent area of deletion, and it was significantly correlated with aggressive and metastatic behaviour of the disease and also with poorly differentiated tumours (Elo et al, 1997).There are several candidate genes putatively involved in prostatic carcinogenesis located distally at 16q. The 17HSD type 2 gene (HSD17B2), located at 16q24.1-q24.2, encodes the 17β-hydroxysteroid dehydrogenase (17HSD) type 2 isoenzyme, which Summary Loss of heterozygosity at chromosome arm 16q is a frequent event in human prostate cancer. In this study, loss of heterozygosity at 16q was studied in 44 prostate ca...

17β-Estradiol upregulates and activates WOX1/WWOXv1 and WOX2/WWOXv2 in vitro: potential role in cancerous progression of breast and prostate to a premetastatic state in vivo

“…That is, WOX1 protein may participate in inhibiting cancer cell metastasis. This notion is supported by the observations that distinct deleted regions on chromosome segment 16q23-24, encoding WWOX/FOR2/WOX1, are associated with metastases in prostate and breast cancers (Caligo et al, 1998;Elo et al, 1999;Li et al, 1999).…”

Allelic losses at 8p, 10q, 11p, 13q, 16q, 17p, and 18q in prostatic carcinomas: The impact of zonal location, Gleason grade, and tumour multifocality

“…12,25,49 Furthermore, additional sites of deletion more telomeric to 16q22 have been reported and it seems as if the long arm of chromosome 16 harbours multiple tumour suppressor genes. 12,13,25 Some of these investigators found a signi®cant correlation between 16q losses and metastatic and aggressive behaviour of prostate cancers. 11 ± 13 In the present study, allelic imbalance at 16q was not signi®cantly associated with higher Gleason scores, which is in concordance with the ®ndings by Godfrey and co-workers.…”

High-Resolution Analysis of Paraffin-Embedded and Formalin-Fixed Prostate Tumors Using Comparative Genomic Hybridization to Genomic Microarrays

“…Moreover, it is increasingly evident that differing clinical behavior of histologically similar tumors is because of distinct and recurrent patterns of genomic alterations and that these may define distinct subsets of disease and thus be prognostic. [1][2][3][4] aCGH is ideally suited to delineating these genomic differences and for the development of biomarkers. However, the coupling of aCGH and clinical data for biomarker discovery and disease stratification requires patients with significant clinical follow-up, meaning that in most cases archived tumor material must be used to identify associations between copy number changes and clinical outcome.…”