Somatic Copy Number Alterations and Associated Genes in Clear-Cell Renal-Cell Carcinoma in Brazilian Patients.
Somatic copy number aberrations (CNAs) have been associated with clear-cell renal carcinoma (ccRCC) pathogenesis and are a potential source of new diagnostic, prognostic and therapeutic biomarkers. Recurrent CNAs include loss of chromosome arms 3p, 14q, 9p, and gains of 5q and 8q. Some of these regional CNAs are suspected of altering gene expression and could influence clinical outcomes. Despite many studies of CNAs in RCC, there are currently no descriptions of genomic copy number alterations in a Brazilian ccRCC cohort. This study was designed to evaluate the chromosomal profile of CNAs in Brazilian ccRCC tumors and explore clinical associations. A total of 92 ccRCC Brazilian patients that underwent nephrectomy at Barretos Cancer Hospital were analyzed for CNAs by array comparative genomic hybridization. Most patients in the cohort had early-stage localized disease. The most significant alterations were loss of 3p (87.3%), 14q (35.8%), 6q (29.3%), 9p (28.6%) and 10q (25.0%), and gains of 5q (59.7%), 7p (29.3%) and 16q (20.6%). Bioinformatics analysis revealed 19 genes mapping to CNA significant regions, including SETD2, BAP1, FLT4, PTEN, FGFR4 and NSD1. Moreover, gain of 5q34-q35.3 (FLT4 and NSD1) and loss of 6q23.2-q23.3 (MYB) and 9p21.3 (MLLT3) had gene expression levels that correlated with TCGA data and was also associated with advanced disease features, such as larger tumors, Fuhrman 3, metastasis at diagnosis and death. The loss of region 14q22.1 which encompasses the NIN gene was associated with poor overall survival. Overall, this study provides the first CNA landscape of Brazilian patients and pinpoints genomic regions and specific genes worthy of more detailed investigations. Our results highlight important genes that are associated with copy number changes involving large chromosomal regions that are potentially related to ccRCC tumorigenesis and disease biology for future clinical investigations.
['Fernandes|Flávia Gonçalves|FG|0000-0002-2852-467X', 'Silveira|Henrique Cesar Santejo|HCS|0000-0001-8607-6206', 'Júnior|João Neif Antonio|JNA|', 'da Silveira|Rosana Antunes|RA|', 'Zucca|Luis Eduardo|LE|', 'Cárcano|Flavio Mavignier|FM|', 'Sanches|André Octavio Nicolau|AON|', 'Neder|Luciano|L|', 'Scapulatempo-Neto|Cristovam|C|', 'Serrano|Sergio Vicente|SV|', 'Jonasch|Eric|E|', 'Reis|Rui Manuel|RM|0000-0002-9639-7940', 'Evangelista|Adriane Feijó|AF|0000-0002-4731-2082']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D001938:Brazil D002292:Carcinoma, Renal Cell D002883:Chromosomes, Human, Pair 14 D003198:Computer Simulation D056915:DNA Copy Number Variations D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D007680:Kidney Neoplasms D008297:Male D008875:Middle Aged D015999:Multivariate Analysis D016019:Survival Analysis D059467:Transcriptome D055815:Young Adult
clear-cell renal-cell carcinoma copy number aberrations bioinformatics Brazilian population