Validation and Implementation of BRCA1/2 Variant Screening in Ovarian Tumor Tissue

Publication date: Available online 21 June 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Marthe M. de Jonge, Dina Ruano, Ronald van Eijk, Nienke van der Stoep, Maartje Nielsen, Juul T. Wijnen, Natalja T. ter Haar, Astrid Baalbergen, Monique E.M.M. Bos, Marjolein J. Kagie, Maaike P.G. Vreeswijk, Katja N. Gaarenstroom, Judith R. Kroep, Vincent T.H.B.M. Smit, Tjalling Bosse, Tom van Wezel, Christi J. van AsperenAbstractBRCA1/2 variant analysis in tumor tissue could streamline the referral of patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer to genetic counselors and select patients who benefit most from targeted treatment. We investigated the sensitivity of BRCA1/2 variant analysis in formalin-fixed, paraffin-embedded tumor tissue using a combination of next-generation sequencing and copy number variant multiplex ligation-dependent probe amplification. After optimization using a training cohort of known BRCA1/2 mutation carriers, validation was performed in a prospective cohort (Clinical implementation Of BRCA1/2 screening in ovarian tumor tissue: COBRA-cohort) in which screening of BRCA1/2 tumor DNA and leukocyte germline DNA was performed in parallel. BRCA1 promoter hypermethylation and pedigree analysis were also performed. In the training cohort 45 of 46 germline BRCA1/2 variants were detected (sensitivity 98%). In the COBRA cohort (n=62), all six germline variants were identified (sensitivity 100%), together with five somatic BRCA1/...
Source: The Journal of Molecular Diagnostics - Category: Pathology Source Type: research