title: The chromatin remodeling gene ARID1A is a new prognostic marker in clear cell renal cell carcinoma.
abstract: Clear cell renal cell carcinoma (ccRCC) is the most common tumor of the adult kidney, with an increasing rate of incidence. Recently, exome sequencing studies have revealed that the SWI/SNF (switch/sucrose nonfermentable) members PBRM1 and ARID1A are mutated in ccRCC, and it has also been suggested that aberrant chromatin regulation is a key step in kidney cancer pathogenesis. Herein, we show that down-regulation of another SW/SNF component, ARID1A, occurs frequently in ccRCC. We detected copy number loss of ARID1A in 16% of patients with ccRCC. Immunohistochemistry indicated that 67% of ccRCC (53 of 79) had significantly lower expression of BAF250a, the protein product of ARID1A, than did the matched normal kidney cortex. In parallel, we conducted in silico mRNA expression analysis on 404 ccRCC tumors and 167 normal kidney cortex samples using publicly available databases and confirmed significant down-regulation of ARID1A in 68.8% of patients. We also show that decreased BAF250a protein and ARID1A mRNA expression correlate with tumor stage and grade. Our results indicate that both the protein and mRNA levels of ARID1A are statistically significant prognostic markers for ccRCC. Even after controlling for other confounders in the multivariate analysis, BAF250 retained its prognostic significance. BAF250a IHC is easy to perform and represents a potential biomarker that could be incorporated in laboratory practice to enhance the accuracy of the existing prognostic models.
authors: Department of Laboratory Medicine and Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario M5B 1WB, Canada.
authors: Zsuzsanna
authors: Z
authors: Lichner
authors: Andreas
authors: A
authors: Scorilas
authors: Nicole M A
authors: NM
authors: White
authors: Andrew H
authors: AH
authors: Girgis
authors: Lora
authors: L
authors: Rotstein
authors: Kimberly C
authors: KC
authors: Wiegand
authors: Ashraf
authors: A
authors: Latif
authors: Christina
authors: C
authors: Chow
authors: David
authors: D
authors: Huntsman
authors: George M
authors: GM
authors: Yousef
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D004268:DNA-Binding Proteins; D018572:Disease-Free Survival; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C112476:ARID1A protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors