PURPOSE: We identified regions of DNA copy number changes that are significantly associated with metastasis and clinical outcome in patients with clear cell renal cell carcinoma. MATERIALS AND METHODS: We analyzed 53 primary clear cell renal cell carcinomas, including 31 metastasized and 22 nonmetastasized tumors, by array comparative genomic hybridization with a median resolution of 1 to 1.5 Mbp. To validate copy number aberrations with potential prognostic value we performed fluorescence in situ hybridization analysis using commercially available fluorescent probes. RESULTS: We identified 5 recurrent chromosomal aberrations that were significantly associated with metastasis, including gains of 1q21.3, 12q13.12, 12q13.3q14.1 and 20q11.21q13.2, and loss of 9p21.3p24.1. The most prominent of them with the highest OR for metastatic risk were loss of 9p21.3p24.1, and gains of 1q21.3 and 20q11.21q13.32. Eight alterations involving chromosomes 7, 9, 12, 16 and 20 significantly correlated with shortened cancer specific survival. The lowest p values on Kaplan-Meier analysis showed losses of 9p21.3p24.1 and 9q32q33.1, and gains of 7q36.3 and 20q11.21q13.32. Fluorescence in situ hybridization done in the same cohort for the 4 select regions 1q21.3, 7q36.3, 9p21.3p24.1 and 20q11.21q13.32 clearly confirmed the results of array comparative genomic hybridization. CONCLUSIONS: Data suggest that specific chromosomal alterations in clear cell renal cell carcinoma can be used to predict metastasis and cancer specific survival in patients with clear cell renal cell carcinoma. It seems possible to design a combined fluorescence in situ hybridization assay based on these genetic targets for outcome prediction, which can be used for routine diagnostics.
PURPOSE: We identified regions of DNA copy number changes that are significantly associated with metastasis and clinical outcome in patients with clear cell renal cell carcinoma. MATERIALS AND METHODS: We analyzed 53 primary clear cell renal cell carcinomas, including 31 metastasized and 22 nonmetastasized tumors, by array comparative genomic hybridization with a median resolution of 1 to 1.5 Mbp. To validate copy number aberrations with potential prognostic value we performed fluorescence in situ hybridization analysis using commercially available fluorescent probes. RESULTS: We identified 5 recurrent chromosomal aberrations that were significantly associated with metastasis, including gains of 1q21.3, 12q13.12, 12q13.3q14.1 and 20q11.21q13.2, and loss of 9p21.3p24.1. The most prominent of them with the highest OR for metastatic risk were loss of 9p21.3p24.1, and gains of 1q21.3 and 20q11.21q13.32. Eight alterations involving chromosomes 7, 9, 12, 16 and 20 significantly correlated with shortened cancer specific survival. The lowest p values on Kaplan-Meier analysis showed losses of 9p21.3p24.1 and 9q32q33.1, and gains of 7q36.3 and 20q11.21q13.32. Fluorescence in situ hybridization done in the same cohort for the 4 select regions 1q21.3, 7q36.3, 9p21.3p24.1 and 20q11.21q13.32 clearly confirmed the results of array comparative genomic hybridization. CONCLUSIONS: Data suggest that specific chromosomal alterations in clear cell renal cell carcinoma can be used to predict metastasis and cancer specific survival in patients with clear cell renal cell carcinoma. It seems possible to design a combined fluorescence in situ hybridization assay based on these genetic targets for outcome prediction, which can be used for routine diagnostics.
Authors: A Ari Hakimi; Roy Mano; Giovanni Ciriello; Mithat Gonen; Nina Mikkilineni; John P Sfakianos; Philip H Kim; Robert J Motzer; Paul Russo; Victor E Reuter; James J Hsieh; Irina Ostrovnaya Journal: J Urol Date: 2014-02-08 Impact factor: 7.450
Authors: Sakshi Gulati; Pierre Martinez; Tejal Joshi; Nicolai Juul Birkbak; Claudio R Santos; Andrew J Rowan; Lisa Pickering; Martin Gore; James Larkin; Zoltan Szallasi; Paul A Bates; Charles Swanton; Marco Gerlinger Journal: Eur Urol Date: 2014-07-19 Impact factor: 20.096
Authors: Ismail El-Mokadem; John Fitzpatrick; Bhavan Rai; J Cunningham; Norman Pratt; Stewart Fleming; Ghulam Nabi Journal: Biomed Res Int Date: 2014-04-30 Impact factor: 3.411
Authors: Hala Girgis; Olena Masui; Nicole Ma White; Andreas Scorilas; Fabio Rotondo; Annetta Seivwright; Manal Gabril; Emily R Filter; Andrew Ha Girgis; Georg A Bjarnason; Michael As Jewett; Andrew Evans; Sahar Al-Haddad; Kw Michael Siu; George M Yousef Journal: Mol Cancer Date: 2014-05-05 Impact factor: 27.401
Authors: J Sanjmyatav; S Matthes; M Muehr; D Sava; M Sternal; H Wunderlich; M Gajda; M-O Grimm; K Junker Journal: Br J Cancer Date: 2014-03-25 Impact factor: 7.640