Extensive analysis of the 13q14 region in human prostate tumors: DNA analysis and quantitative expression of genes lying in the interval of deletion

• Published in: The Prostate Vol. 57; no. 1; pp. 39 - 50
• Main Authors: Latil, Alain, Chêne, Laurent, Mangin, Philippe, Fournier, Georges, Berthon, Philippe, Cussenot, Olivier
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-09-2003
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Chromosomes, Human, Pair 13; DNA, Neoplasm - analysis; Gene Expression Regulation, Neoplastic; human prostate cancer; Humans; Loss of Heterozygosity; Male; Neoplasm Staging; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; real-time quantitative RT-PCR assay; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - analysis; RNA, Neoplasm - analysis; target genes reduced expression
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.10272

BACKGROUND
Loss of heterozygosity (LOH) on chromosome arm 13q14 is one of the most consistent genetic alterations in sporadic prostate cancer. This alteration may be involved in prostate oncogenesis through inactivation of one or more tumor suppressor genes (TSGs). Candidate gene expression is an approach to focus the search for TSGs in this region.
METHODS
We tested 41 human sporadic prostate tumors for 13q14 LOH by using seven polymorphic markers overlapping the critical region and used a real‐time quantitative RT‐PCR assay to study the same tumors for expression of the 31 genes located in this genomic region (localized by the Human Genome Project Working Draft).
RESULTS
Allelic loss on at least one locus was found in 18 (41%) of the 41 tumor DNAs. Only four genes (ITM2B, CHC1L, KIAA0970, and LOC51131), located in the region most frequently deleted in prostate carcinoma, showed a significant difference in expression between normal and neoplastic prostate tissues.
CONCLUSIONS
Given their location in the LOH hotspot, as indicated by our genomic analysis, ITM2B, CHC1L, KIAA0970, and LOC51131 are candidate tumor suppressor genes in this region. ITM2B that showed a significant association (P < 0.005) between expression and LOH at the corresponding locus could, furthermore, be the main target of the observed LOH at 13q in prostate tumors. Prostate 57: 39–50, 2003. © 2003 Wiley‐Liss, Inc.