Abstract 1145P
Background
PARP inhibitors are used for treatment of tumors lacking function of the double-strand DNA break repair proteins BRCA1 or BRCA2 and are already approved for several cancer types. Thus, it is clinically crucial to determine germline as well as somatic BRCA1/2 mutations in those patients. The amplicon-based Oncomine BRCA1 and BRCA2 Assay is a test routinely used in diagnostics with FFPE specimens. The assay is validated for the detection of mutations, however, data on its performance in detecting large genomic rearrangements in FFPE tissue, is scarce.
Methods
We cross-validated Oncomine BRCA1 and BRCA2 Assay in blood samples and/or FFPE tissue with multiplex ligation-dependent probe amplification (MLPA) for exon deletions and OncoScan, and an in-house hybridization-based target capture NGS assay (MelArray) with a customized pipeline for the detection of loss of heterozygosity (LOH) and heterozygous versus complete gene loss.
Results
The Oncomine BRCA1 and BRCA2 Assay could detect both exon deletion and mono- and bi-allelic losses of the BRCA1/2 genes in samples with tumor content greater than 40%. We show that the therapeutically relevant large genomic rearrangements are reliably detected with the amplicon-based Oncomine BRCA1 and BRCA2 Assay in FFPE tumor tissue.
Conclusions
Based on our data, we suggest somatic BRCA testing as standard diagnostic prescreening prior to germline BRCA testing. Thus, a rapid, reliable and affordable sBRCA testing could be used in the future as standard analysis after diagnosis with ovarian, breast, pancreatic and prostate cancer in routine diagnostics. This will immensely shorten the time for treatment decision, especially for patients without BRCA1/2 alterations since generally only patients with sBRCA mutations will be referred to the more time consuming genetic counselling and germline (gBRCA) testing.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
University Hospital Zurich.
Funding
Innovation Pool of the University Hospital Zurich # INOV00102.
Disclosure
All authors have declared no conflicts of interest.