Prostate cancer is characterized by a high incidence, great variation in the length of the latent period and uncertainty in the outcome. Moreover, blood PSA screening has resulted in over-diagnosis, so that many patients have clinically insignificant disease. Currently, treatment at first diagnosis is based on predictive nomograms, which integrate detailed histopathology with clinical data to determine an overall risk score. To date, there are no biomarkers that reliably work on diagnostic needle core tissue sections that can determine which intermediate risk prostate cancers will remain indolent and which tumors are likely to be more aggressive. Our recent data suggest that tumors with the poorest outcome have both PTEN loss and fusions of the TMPRSS2-ERG genes with recurrent copy number variation (CNV) affecting other regions of the genome. The objective of this project is to identify a series of new genetic biomarkers for improved prognostic assessment using a cohort of 150 patients with known clinical outcome. We will first determine which tumors have acquired the PTEN and TMPRSS2-ERG gene biomarkers using a combination of FISH, immunohistochemistry and mutation analysis techniques. Then, array-CGH technique will be used to compare the overall CNV profiles in tumors with both of the PTEN and TMPRSS2-ERG genetic biomarkers to those tumors without either aberration. Bioinformatic analyses will then be used to select the strongest candidate genes in the common CNV regions in this tumor subgroup associated with advanced cancers and with disease progression. These genes will be used as highly informative FISH probes panel to evaluate prognostic risk in prostate cancer. (AU)
Articles published in Agência FAPESP Newsletter about the research grant:
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PATEL, PALAK G.;
OKELLO, JOHN B.;
GUEDES, LIANA B.;
REIS, RODOLFO B.;
LOTAN, TAMARA L.;
SQUIRE, JEREMY A.;
PENG, YINGWEI P.;
SIEMENS, D. ROBERT;
BERMAN, DAVID M.
Risk Stratification of Prostate Cancer Through Quantitative Assessment of PTEN Loss (qPTEN).
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE,
Web of Science Citations: 4.