Copy number alterations of c-MYC and PTEN are prognostic factors for relapse after prostate cancer radiotherapy
| Autor: | Omar Ahmed, Igor Jurisca, Robert G. Bristow, Jeremy A. Squire, Maisa Yoshimoto, Alice Meng, John Thoms, Jenna Sykes, Wan L. Lam, Michael Milosevic, Jennifer A. Locke, Melania Pintilie, Chad A. Malloff, Theo H. van der Kwast, Gaetano Zafarana, Adrian Ishkanian, Varune Rohan Ramnarine |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty DNA Copy Number Variations medicine.medical_treatment Genes myc Loss of Heterozygosity Genomic Instability Loss of heterozygosity Prostate cancer Recurrence Internal medicine medicine Humans PTEN biology business.industry Prostatectomy Hazard ratio PTEN Phosphohydrolase Prostatic Neoplasms Prognosis medicine.disease Radiation therapy Prostate-specific antigen biology.protein business Radiotherapy Image-Guided Comparative genomic hybridization |
| Zdroj: | Cancer. 118:4053-4062 |
| ISSN: | 0008-543X |
| DOI: | 10.1002/cncr.26729 |
| Popis: | Despite the use of PSA, Gleason score, and T-category as prognosticators in intermediate-risk prostate cancer, 20-40% of patients will fail local therapy. In order to optimize treatment approaches for intermediate-risk patients, additional genetic prognosticators are needed. Previous reports using array comparative genomic hybridization (aCGH) in radical prostatectomy cohorts suggested a combination of allelic loss of the PTEN gene on 10q and allelic gain of the c-MYC gene on 8q were associated with metastatic disease. We tested whether copy number alterations (CNAs) in PTEN (allelic loss) and c-MYC (allelic gain) were associated with biochemical relapse following modern-era, image-guided radiotherapy (mean dose 76.4 Gy). We used aCGH analyses validated by fluorescence in-situ hybridization (FISH) of DNA was derived from frozen, pre-treatment biopsies in 126 intermediate-risk prostate cancer patients. Patients whose tumors had CNAs in both PTEN and c-MYC had significantly increased genetic instability (percent genome alteration; PGA) compared to tumors with normal PTEN and c-MYC status (p < 0.0001). We demonstrate that c-MYC gain alone, or combined c-MYC gain and PTEN loss, were increasingly prognostic for relapse on multivariable analyses (hazard ratios (HR) of 2.58/p = 0.005 and 3.21/p = 0.0004; respectively). Triaging patients by the use of CNAs within pre-treatment biopsies may allow for better use of systemic therapies to target sub-clinical metastases or locally recurrent disease and improve clinical outcomes. |
| Databáze: | OpenAIRE |
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