Τίτλος:
The chromatin remodeling gene ARID1A is a new prognostic marker in clear cell renal cell carcinoma
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. Copyright © 2013 American Society for Investigative Pathology.
Συγγραφείς:
Lichner, Z.
Scorilas, A.
White, N.M.A.
Girgis, A.H.
Rotstein, L.
Wiegand, K.C.
Latif, A.
Chow, C.
Huntsman, D.
Yousef, G.M.
Περιοδικό:
American Journal of Pathology
Λέξεις-κλειδιά:
messenger RNA; retinoblastoma binding protein 2, article; cancer prognosis; cancer staging; cancer survival; carcinogenesis; chromatin assembly and disassembly; computer model; controlled study; copy number variation; down regulation; exome; female; gene expression; gene loss; gene mutation; gene sequence; human; human cell; human tissue; immunohistochemistry; kidney carcinoma; kidney cortex; major clinical study; male; priority journal, Adult; Carcinoma, Renal Cell; Chromatin Assembly and Disassembly; Disease-Free Survival; DNA Copy Number Variations; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Genes, Neoplasm; Humans; Kidney; Kidney Neoplasms; Male; Nuclear Proteins; Prognosis; RNA, Messenger; Transcription Factors; Tumor Markers, Biological
DOI:
10.1016/j.ajpath.2013.01.007
