Abstract
BackgroundDeregulation of the RNA polymerase III specific TFIIIB subunit BRF2 occurs in subtypes of human cancers. However, correlations between BRF2 alterations and clinical outcomes in breast cancer are limited. We conducted this review to analyze BRF2 alterations in genomic data sets housed in Oncomine and cBioPortal to identify potential correlations between BRF2 alterations and clinical outcomes.MethodsThe authors queried both Oncomine and cBioPortal for alterations in BRF2 in human cancers and performed meta-analyses identifying significant correlations between BRF2 and clinical outcomes in invasive breast cancer (IBC).ResultsA meta cancer outlier profile analysis (COPA) of 715 data sets (86,733 samples) in Oncomine identified BRF2 as overexpressed in 60% of breast cancer data sets. COPA scores in IBC data sets (3594 patients) are comparable for HER2 (24.211, median gene rank 60) and BRF2 (29.656, median gene rank 36.5). Overall survival in IBC patients with BRF2 alterations (21%) is significantly decreased (p = 9.332e-3). IBC patients with BRF2 alterations aged 46 to 50 have a significantly poor survival outcome (p = 7.093e-3). Strikingly, in metastatic breast cancer, BRF2 is altered in 33% of women aged 45–50. BRF2 deletions are predominant in this age group.ConclusionThis study suggests BRF2 may be an prognostic biomarker in invasive breast carcinoma.
Highlights
Deregulation of the RNA polymerase III specific TFIIIB subunit BRF2 occurs in subtypes of human cancers
A disease summary analysis for BRF2 was performed under stringent conditions as requiring a threshold p-value of 1E-4, a fold-change of 2 for BRF2 gene expression compared to the controls, and a gene rank percentile of top 10%
Using a threshold p-value of 1E-4, a 2 a fold-change for BRF2 gene expression compared to the controls, and a gene rank percentile of 10%, we demonstrate that BRF2 is both over- and under-expressed across the analyzed human cancers (Fig. 1a)
Summary
Deregulation of the RNA polymerase III specific TFIIIB subunit BRF2 occurs in subtypes of human cancers. Correlations between BRF2 alterations and clinical outcomes in breast cancer are limited. In 2020, the leading sites for new cancers and deaths in the United States (U.S.) will be breast, prostate, lung, and colorectal cancers [1]. For U.S women, breast cancer is the second leading cause of cancer-related deaths, second to lung [2]. Regulation of RNA pol III recognizes both gene- internal and external promoters and requires two forms of TFIIIB [3, 5]. RNA Transcription from gene internal (type 2) RNA pol III promoters requires a form of TFIIIB, which includes TBP, BDP1, and BRF1. In the case of transcription from type 3 RNA pol III promoters, the form of TFIIIB
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