Novel Reference Materials Meet Needs of Labs Testing for BRCA1/2 Gene Variants

Large genomic rearrangements (LGRs), which involve deletions, duplications, and insertions often affecting whole exons, account for up to 27% of BRCA1 and 5% of BRCA2 disease-causing mutations in populations with a strong founder effect. LGRs, typically pathogenic, are difficult to detect and are often overlooked by PCR-based and targeted NGS assays that do not identify partial or complete exon losses or gains. Nevertheless, accurately detecting BRCA1 or BRCA2 pathogenic variants is crucial for clinical disease management, particularly regarding patients' eligibility for PARP inhibitor treatments.

LGC Clinical Diagnostics (Gaithersburg, MD, USA) has released its Seraseq BRCA1/2 Large Genomic Rearrangements Reference Materials to assist clinical laboratories in developing, characterizing, validating, and routinely assessing NGS assays. These innovative reference materials are designed to meet the needs of clinical laboratories testing for BRCA1/2 gene variants at both somatic and germline levels. They contain 20 pathogenic BRCA1 and BRCA2 variants, including 11 exon-level large rearrangements, with 10 variants each in BRCA1 and BRCA2.

These variants range in size from single nucleotide variants (SNVs) to insertions and/or deletions over 500 bp, encompassing missense, nonsense, frameshift, stop-gain/loss, splice-site, and insertion/deletion of partial or up to two exons, resulting in diverse alterations at the amino acid level. The products combine BRCA variants in the well-characterized GM24385 genomic background at clinically relevant allele frequencies, precisely quantitated by digital PCR and further analyzed by NGS. They are available in either formalin-fixed, paraffin-embedded (FFPE) format (for somatic testing) or purified genomic DNA (gDNA) format (for germline or somatic testing).

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