NDLI: Identification of BRCA1 Deficiency Using Multi-Analyte Estimation of BRCA1 and Its Repressors in FFPE Tumor Samples from Patients with Triple Negative Breast Cancer.

Content Provider	Directory of Open Access Journals (DOAJ)
Author	Aruna Korlimarla Jyothi S. Prabhu Jose Remacle Savitha Rajarajan Uma Raja Anupama C. E. B. S. Srinath Suraj Manjunath Gopinath K. S. Marjorrie Correa Prasad M. S. N. T. S. Sridhar
Abstract	Apart from germ-line BRCA1-mutated breast cancers, a significant proportion of women with sporadic triple negative breast cancer (TNBC) sub-type are known to harbour varying levels of BRCA1-dysfuction. There is currently no established diagnostic method to identify these patients.The analysis was performed on 183 primary breast cancer tumor specimens from our longitudinal case-series archived as formalin-fixed-paraffin-embedded (FFPE) blocks comprising 71 TNBCs and 112 Hormone receptor positive HER2 negative (HR+HER2-) tumors. Transcript levels of BRCA1 and two of its repressors ID4 and microRNA182 were determined by TaqMan quantitative PCR. BRCA1 protein was detected immunohistochemically with the MS110 antibody.The representation of BRCA1 and its repressor ID4 as a ratio led to improved separation of TNBCs from HR+HER2- compared to either measure by itself. We then dichotomised the continuous distribution of each of the three measurements (Protein, MIRNA and transcript:repressor ratio) into categories of deficient (0) and adequate (1). A composite BRCA1 Deficiency Score (BDS) was computed by the addition of the score for all three measures. Samples deficient on 2 or more measures were deemed to be BRCA1 deficient; and 40% of all TNBCs met this criterion.We propose here a simple multi-level assay of BRCA1 deficiency using the BRCA1:ID4 ratio as a critical parameter that can be performed on FFPE samples in clinical laboratories by the estimation of only 3 bio-markers. The ease of testing will hopefully encourage adoption and clinical validation.
e-ISSN	19326203
DOI	10.1371/journal.pone.0153113
Journal	PLoS ONE
Issue Number	4
Volume Number	11
Language	English
Publisher	Public Library of Science (PLoS)
Publisher Date	2016-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Medicine Science
Content Type	Text
Resource Type	Article

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