BRCAtesting on buccal swab to improve access to healthcare and cancer prevention: a performance evaluation

Abstract

ObjectiveBRCA1/2 (BRCA) genetic testing allows patients with high-grade serous ovarian cancer to receive appropriate medical management with molecular target therapy and prevention strategies. Most of theBRCAsequencing methods use blood as the primary source of germline DNA. Buccal swab emerged as an alternative collection device due to its convenient and non-invasive characteristics. This study assessed the suitability of buccal swabs as the DNA source in next-generation sequencing-basedBRCAgenotyping.MethodsMatched buccal swabs and blood samples were collected from 51 patients with high-grade serous ovarian cancer, including 29BRCA-mutated patients, from June to December 2021. Buccal swabs were self-collected using COPAN FLOQSwabs hDNA Free.BRCAgenes were amplified using Devyser’sBRCAnext-generation sequencing kit and sequenced on the Illumina MiSeq platform. We evaluated collection and extraction procedures, amplification and sequencing performances, coverage data, blood/swab variant calling concordance, and interpretation.ResultsComparable sequencing parameters were observed between the two sample types in term of mean total number of reads passing filter for indexed sample (p>0.05) and sequencing coverage distribution, with a widespread overlap of mean depth of coverage/target region between blood and swab samples. An overall concordance of 100% in both polymorphisms and pathogenic variants calling between the two DNA sources were observed, including the copy number variation prediction.ConclusionsData from this study support the use of buccal swabs as an alternative source of DNA forBRCAevaluation. The use of this alternative delivery mode ofBRCAtesting may facilitate access to care without compromising patient outcomes.