Investigation of Clinically Useful Genomic Biomarkers in Prostate Cancer

• Grant number: 15/09111-5
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2016
• End date: January 31, 2018
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Jeremy Andrew Squire
• Grantee: Jeremy Andrew Squire
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Alfredo Ribeiro da Silva ; Fabiano Pinto Saggioro ; Rodolfo Borges dos Reis ; Silvana Giuliatti

Abstract

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)

Scientific publications

(6)

(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)

YOSHIMOTO, MAISA; LUDKOVSKI, OLGA; GOOD, JENNIFER; PEREIRA, CIRO; GOODING, ROBERT J.; MCGOWAN-JORDAN, JEAN; BOAG, ALEXANDER; EVANS, ANDREW; TSAO, MING-SOUND; NUIN, PAULO; et al. Use of multicolor fluorescence in situ hybridization to detect deletions in clinical tissue sections. LABORATORY INVESTIGATION, v. 98, n. 4, p. 403-413, APR 2018. (15/09111-5)

JAMASPISHVILI, TAMARA; PATEL, PALAK; NIU, YI; VIDOTTO, THIAGO; CAVEN, ISABELLE; LIVERGANT, RACHEL; FU, WINNIE; OUELLET, VERONIQUE; PICANCO, CLARISSA; KOTI, MADHURI; et al. QUANTITATIVE MEASUREMENT OF PTEN LOSS IMPROVES RISK ASSESSMENT IN PROSTATE CANCER. JOURNAL OF UROLOGY, v. 201, n. 4, p. 1-pg., 2019-04-01. (15/09111-5)

HARMON, STEPHANIE A.; PATEL, PALAK G.; SANFORD, THOMAS H.; CAVEN, ISABELLE; ISEMAN, RACHAEL; VIDOTTO, THIAGO; PICANCO, CLARISSA; SQUIRE, JEREMY A.; MASOUDI, SAMIRA; MEHRALIVAND, SHERIF; et al. High throughput assessment of biomarkers in tissue microarrays using artificial intelligence: PTEN loss as a proof-of-principle in multi-center prostate cancer cohorts. MODERN PATHOLOGY, v. 34, n. 2, SEP 2020. (15/09111-5, 17/08614-9, 15/22785-5)

JAMASPISHVILI, TAMARA; PATEL, PALAK G.; NIU, YI; VIDOTTO, THIAGO; CAVEN, ISABELLE; LIVERGANT, RACHEL; FU, WINNIE; KAWASHIMA, ATSUNARI; HOW, NATHAN; OKELLO, JOHN B.; et al. Risk Stratification of Prostate Cancer Through Quantitative Assessment of PTEN Loss (qPTEN). JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, v. 112, n. 11, p. 1098-1104, NOV 2020. (15/09111-5)

VIDOTTO, THIAGO; MELO, CAMILA MORAIS; CASTELLI, ERICK; KOTI, MADHURI; DOS REIS, RODOLFO BORGES; SQUIRE, JEREMY A.. Emerging role of PTEN loss in evasion of the immune response to tumours. BRITISH JOURNAL OF CANCER, v. 122, n. 12, APR 2020. (15/09111-5, 17/08614-9, 15/22785-5)

VIDOTTO, THIAGO; TIEZZI, DANIEL GUIMARAES; SQUIRE, JEREMY A.. Distinct subtypes of genomic PTEN deletion size influence the landscape of aneuploidy and outcome in prostate cancer. MOLECULAR CYTOGENETICS, v. 11, JAN 3 2018. (15/09111-5, 15/22785-5, 16/02730-4)