Comparative Genomic Hybridization: The Profile Of Chromosomal Imbalances In Renal Cell Carcinoma

Objective: To characterize the profiles of chromosome imbalance of renal cell carcinoma by Comparative Genomic Hybridization (CGH).And compare the different alterations among the histological subtypes , grading and clinical staging.Methods: Forty-six primary renal cell carcinoma for which formalin-fixed, paraffin-embedded samples were available were collected from the archives of the Department of Pathology. Including10 clear cell renal cell carcinoma cases, 13 papillary renal cell carcinoma cases, 12 chromophobe renal cell carcinoma cases, 9 renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions cases, and 2 undifferentiated renal carcinoma cases were collected for the study. A set of representative hematoxylin and eosin stained slides were marked with identifying numbers and reviewed individually by two pathologists blinded to all clinical information according to 2004 WHO Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs.We screened DNA copy number changes in whole genomes by CGH in 46 primary renal cell carcinoma. Analyse according to histological type, grading,clinical staging, respectively. All data were analyzed using the SPSS 13.0 software package.Results: 1. 46 cases with renal cell carcinoma showed evidence of increased or decreased DNA sequence copy numbers involving one or more regions of the genome. The frequently gained chromosome arms of RCC were 7q,16p,20q, and the frequently lost chromosome arms of RCC were 1p,3p,13q,14q,8p. 2. Different histological type of RCC showed different abnormality of DNA copy number. (1) The frequently gained chromosome arms of CCRCC were 7q,16p,5q; the frequently lost chromosome arms were 3p,8p,1p, 4p,4q,9p. (2) The frequently gained chromosome arms of PRCC were 7p,7q,12q,16q,20p,20q; the frequently lost chromosome arms were 14q,18q,13q,3p,4p,6q. (3) The frequently gained chromosome arms of ChrRCC were 1q,3q,1p; the frequently lost chromosome arms were1p,17p,10p,13p,2q,8p. Gains of 1q21-23 significantly correlated with ChrRCC and sarcomatoid variants ChrRCC type (P=0.010). (4) The frequently gained chromosome arms of Xp11.2RCC were Xp,7q,12q,8p,8q,16q,17p,17q,20q; the frequently lost chromosome arms were3p, 9q,14q. (5) The frequently gained chromosome arms of UnRCC were 1p,1q,3q,8p,16q; the frequently lost chromosome arms were2p,2q,3p,5p,6p,11q,17p,17q,20p. 3. Gains of 5q,7q,20q and losses of 9q were significantly correlated with clinical staging (P=0.002, P=0.007). 4. 7q was frequently gained in grade 1-2 than 3-4 (nuclear grade of Fuhrman system) of CCRCC and PRCC (P=0.045).Conclusions:(1)7q,16p,2Qq gained and 1 p,3p,13q,14q,8p losses are correlated with RCC. (2) gains of Sq and 7q may indicated prognosis of RCC be favourable; gains of 20q and losses of 9q Enay indicated poor prognosis of RCC.(3)gains of 7q is correkated with low grade of CCRCC and PRCC,and indicated be correlated with prognosis.