High-resolution array CGH identifies novel regions of genomic alteration in intermediate-risk prostate cancer.
Prostate
; 69(10): 1091-100, 2009 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-19350549
ABSTRACT
Approximately one-third of prostate cancer patients present with intermediate risk disease. Interestingly, while this risk group is clinically well defined, it demonstrates the most significant heterogeneity in PSA-based biochemical outcome. Further, the majority of candidate genes associated with prostate cancer progression have been identified using cell lines, xenograft models, and high-risk androgen-independent or metastatic patient samples. We used a global high-resolution array comparative genomic hybridization (CGH) assay to characterize copy number alterations (CNAs) in intermediate risk prostate cancer. Herein, we show this risk group contains a number of alterations previously associated with high-risk disease (1) deletions at 21q22.2 (TMPRSS2ERG), 16q22-24 (containing CDH1), 13q14.2 (RB1), 10q23.31 (PTEN), 8p21 (NKX3.1); and, (2) amplification at 8q21.3-24.3 (containing c-MYC). In addition, we identified six novel microdeletions at high frequency 1q42.12-q42.3 (33.3%), 5q12.3-13.3 (21%), 20q13.32-13.33 (29.2%), 22q11.21 (25%), 22q12.1 (29.2%), and 22q13.31 (33.3%). Further, we show there is little concordance between CNAs from these clinical samples and those found in commonly used prostate cancer cell models. These unexpected findings suggest that the intermediate-risk category is a crucial cohort warranting further study to determine if a unique molecular fingerprint can predict aggressive versus indolent phenotypes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Adenocarcinoma
/
Análise de Sequência com Séries de Oligonucleotídeos
/
Hibridização Genômica Comparativa
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Prostate
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Canadá