Genome-wide analysis of allelic imbalance in prostate cancer using the Affymetrix 50K SNP mapping array.
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.
Tørring
N
N
Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Skejby Sygehus, Aarhus University Hospital, Brendstrupgaardsvej 100, DK-8200 Aarhus, Denmark. nto@ki.au.dk
Borre
M
M
Sørensen
K D
KD
Andersen
C L
CL
Wiuf
C
C
Ørntoft
T F
TF
D022981:Allelic Imbalance; D004273:DNA, Neoplasm / Q000032:analysis; D018628:Gene Dosage; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology
D004273:DNA, Neoplasm