Whole genome scanning identifies genotypes associated with recurrence and metastasis in prostate tumors.
Prostate cancer is the most commonly diagnosed non-cutaneous neoplasm among American males and is the second leading cause of cancer-related death. Prostate specific antigen screening has resulted in earlier disease detection, yet approximately 30% of men will die of metastatic disease. Slow disease progression, an aging population and associated morbidity and mortality underscore the need for improved disease classification and therapies. To address these issues, we analyzed a cohort of patients using array comparative genomic hybridization (aCGH). The cohort comprises 64 patients, half of whom recurred postoperatively. Analysis of the aCGH profiles revealed numerous recurrent genomic copy number aberrations. Specific loss at 8p23.2 was associated with advanced stage disease, and gain at 11q13.1 was found to be predictive of postoperative recurrence independent of stage and grade. Moreover, comparison with an independent set of metastases revealed approximately 40 candidate markers associated with metastatic potential. Copy number aberrations at these loci may define metastatic genotypes.
Paris
Pamela L
PL
Comprehensive Cancer Center, University of California at San Francisco, 94115, USA.
Andaya
Armann
A
Fridlyand
Jane
J
Jain
Ajay N
AN
Weinberg
Vivian
V
Kowbel
David
D
Brebner
John H
JH
Simko
Jeff
J
Watson
J E Vivienne
JE
Volik
Stas
S
Albertson
Donna G
DG
Pinkel
Daniel
D
Alers
Janneke C
JC
van der Kwast
Theodorus H
TH
Vissers
Kees J
KJ
Schroder
Fritz H
FH
Wildhagen
Mark F
MF
Febbo
Phillip G
PG
Chinnaiyan
Arul M
AM
Pienta
Kenneth J
KJ
Carroll
Peter R
PR
Rubin
Mark A
MA
Collins
Colin
C
van Dekken
Herman
H
D014408:Biomarkers, Tumor / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D015331:Cohort Studies; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D009362:Neoplasm Metastasis / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality; D012008:Recurrence
D014408:Biomarkers, Tumor