Integration of high-resolution array comparative genomic hybridization analysis of chromosome 16q with expression array data refines common regions of loss at 16q23-qter and identifies underlying candidate tumor suppressor genes in prostate cancer

• Published in: Oncogene Vol. 23; no. 19; pp. 3487 - 3494
• Main Authors: WATSON, J. E, DOGGETT, Norman A, KOWBEL, David, PINKEL, Daniel, SCHMITT, Lars, SIMKO, Jeffry P, VOLIK, Stanislav, WEINBERG, Vivian K, PARIS, Pamela L, COLLINS, Colin, ALBERTSON, Donna G, ANDAYA, Armann, CHINNAIYAN, Arul, VAN DEKKEN, Herman, GINZINGER, David, HAQQ, Christopher, JAMES, Karen, KAMKAR, Sherwin
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 22.04.2004; Nature Publishing Group
• Subjects: Biological and medical sciences; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chromosomes; Chromosomes, Human, Pair 16; Cloning; DNA microarrays; Fundamental and applied biological sciences. Psychology; Genes, Tumor Suppressor; Genomes; Genomic analysis; Gynecology. Andrology. Obstetrics; Humans; Hybridization; Hybridization analysis; Independent study; Male; Male genital diseases; Medical sciences; Molecular and cellular biology; Nephrology. Urinary tract diseases; Nucleic Acid Hybridization; Prostate cancer; Prostatic Neoplasms - genetics; Transcription; Tumor suppressor genes; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; United States > US; High resolution; Urinary system disease; Prostate disease; array CGH; Loss; Chromosome; Identification; Malignant tumor; chromosome 16q; Gene expression; Carcinogenesis; tumor suppressor genes; Comparative genomic hybridization; Analysis; Candidate gene; Male genital diseases; Prostate cancer; Tumor suppressor gene
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1207474

We have constructed a high-resolution genomic microarray of human chromosome 16q, and used it for comparative genomic hybridization analysis of 16 prostate tumors. We demarcated 10 regions of genomic loss between 16q23.1 and 16qter that occurred in five or more samples. Mining expression array data from four independent studies allowed us to identify 11 genes that were frequently underexpressed in prostate cancer and that co-localized with a region of genomic loss. Quantitative expression analyses of these genes in matched tumor and benign tissue from 13 patients showed that six of these 11 (WWOX, WFDC1, MAF, FOXF1, MVD and the predicted novel transcript Q9H0B8 (NM_031476)) had significant and consistent downregulation in the tumors relative to normal prostate tissue expression making them candidate tumor suppressor genes.