Statistical dissection of genetic pathways involved in prostate carcinogenesis

• Type: Article in International Scientific Journal
• Date: 2006

Authors

Ribeiro, FR (Author) Other; Diep, CB (Author) Other; Carmen Jeronimo (Author) ICBAS; henrique, rmf (Author) ICBAS; Lopes, C (Author) Other; Eknaes, M (Author) Other; Lingjaerde, OC (Author) Other; Lothe, RA (Author) Other; Manuel R Teixeira (Author) ICBAS

Journal

Title: Genes Chromosomes and Cancer

Vol. 45

Pages: 154-163

ISSN: 1045-2257

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 38 Citations

Scopus - 41 Citations

Other information

Authenticus ID: P-004-NDX

DOI: 10.1002/gcc.20279

Abstract (EN): Molecular markers that could stratify prostate cancer patients according to risk of disease progression would allow a significant improvement in the management of this clinically heterogeneous disease. In the present study, we analyzed the genetic profile of a consecutive series of 51 clinically confined prostate carcinomas and 27 benign prostatic hyperplasias using comparative genomic hybridization (CGH). We then added our findings to the existing literature data in order to perform a metaanalysis on a total of 294 prostate cancers with detailed CGH and clinicopathological information, using multivariate statistical methods that included principal component, hierarchical clustering, time of occurrence, and regression analyses. Whereas several genomic imbalances were shared by organ-confined, locally invasive, and metastatic prostate cancers, 6q and 10q losses and 7q and 8q gains were significantly more frequent in patients with extra-prostatic disease. Regression analysis indicated that 8q gain and 13q loss were the best predictors of locally invasive disease, whereas 8q gain and 6q and 10q losses were associated with metastatic disease. We propose a genetic pathway of prostate carcinogenesis with two distinct initiating events, namely, 8p and 13q losses. These primary imbalances are then preferentially followed by 8q gain and 6q, 16q, and 18q losses, which in turn are followed by a set of late events that make recurrent and metastatic prostate cancers genetically more complex. We conclude that significant differences exist in the genetic profile of organ-confined, locally invasive, and advanced prostate cancer and that genetic features may carry prognostic information independently of Gleason grade. (c) 2005 Wiley-Liss, Inc.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10