Abstract 2246: Identification of genomic alterations associated with metastasis and poor prognosis in clear cell renal cell carcinoma

Abstract

Introduction: Clear cell renal cell carcinoma (ccRCC) is the most frequently encountered renal malignancy with a high metastatic potential and the prognosis of patients in this subgroup is very poor. Prognostic parameters which can be used for an individual prognostic evaluation are still not available, So the aim of our study was high resolution screening of genomic imbalances of metastasized and non-metastasized primary ccRCC by array CGH in order to identify regions of DNA copy number changes significantly associated with metastasis and clinical outcome of patients. Methods: We conducted genome-wide copy number profiles in 56 primary ccRCC including 32 metastasized and 24 non-metastasized tumours by array CGH with a median resolution of 2Mbp. The median follow up of the patients was 47 months. Results: Array CGH identified 6 recurrent chromosomal aberrations: gains of 1q21.3, 12q13.11, 12q13.2 and 20q11.21q13.2 and losses of 8p11.23p12 and 9p21.3p24.1, which were significantly associated with metastasis occurrence. In multivariate analysis including these aberrations gains of 1q21.3 and of 20q11.21q13.2 and loss of 9p21.3p24.1 attained as independent predictors for metastasis in our cohort with 81.5% sensitivity and 95.8% specificity of 81.5% and 95.8%, respectively. Kaplan-Meier survival analysis showed that gains on chromosomes 7, 12, 16 and 20q and losses on chromosome 9 have a significant correlation with disease specific survival. Multivariate Cox-regression analysis revealed gains of 7q36.3 and of 20q11.21q13.2 and a loss of 9p21.3p24.1 as independent prognostic factors for patients' outcome of patients. Conclusions: Our data suggest that specific common copy number alterations in ccRCC could serve as independent predictors for metastasis occurrence and cancer specific survival in patients with ccRCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2246.