Genome-wide analysis of allelic imbalance in prostate cancer using the Affymetrix 50K SNP mapping array

• Published in: British journal of cancer Vol. 96; no. 3; pp. 499 - 506
• Main Authors: TØRRING, N, BORRE, M, SØRENSEN, K. D, ANDERSEN, C. L, WIUF, C, ØRNTOFT, T. F
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 12-02-2007
• Subjects: Allelic Imbalance; Androgens; Antigens; Biological and medical sciences; Biopsy; Cancer research; Chromosomes; DNA, Neoplasm - analysis; Gene Dosage; Genome, Human; Genomes; Genotype; Humans; Lasers; Loss of Heterozygosity; Male; Medical research; Medical sciences; Metastasis; Molecular Diagnostics; Nephrology. Urinary tract diseases; Oligonucleotide Array Sequence Analysis - methods; Patients; Polymorphism; Polymorphism, Single Nucleotide; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Urology; Denmark; United States > US; Aarhus Denmark; Urinary system disease; Cancerology; Allelic imbalance; Prostate disease; LOH; SNP; Loss of heterozygosity; Malignant tumor; Single nucleotide polymorphism; Genome; Male genital diseases; Prostate cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6603476

Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer in male subjects in Western countries. The widespread use of prostate-specific antigen (PSA) has increased the detection of this cancer form in earlier stages. Moreover, it has increased the need for new diagnostic procedures to be developed for patient stratification based on risk of progression. We analysed laser-microdissected prostate tumour tissue from 43 patients with histologically verified PCa, using the new high-resolution Affymetrix Mapping 50K single-nucleotide polymorphism array. The results showed six major loss of heterozygosity regions at chromosomes 6q14-16, 8p23-11, 10q23, 13q13-21 and 16q21-24 and a novel region at chromosome 21q22.2, all of which reveal concomitant copy number loss. Tumour development was further characterised by numerous novel genomic regions almost exclusively showing copy number loss. However, tumour progression towards a metastatic stage, as well as poor differentiation, was identified by specific patterns of copy number gains of genomic regions located at chromosomes 8q, 1q, 3q and 7q. Androgen ablation therapy was further characterised by copy gain at chromosomes 2p and 10q. In conclusion, patterns of allelic imbalance were discovered in PCa, consisting allelic loss as an early event in tumour development, and distinct patterns of allelic amplification related to tumour progression and poor differentiation.