Genetic testing of the tumor suppressor genes BRCA1 and BRCA2 allows for the identification of DNA variants which are associated with a significantly elevated lifetime risk of breast, ovarian, pancreatic and prostate cancer.
Large genomic rearrangements (LGRs) include deletions, duplications and/or insertions often involving whole exons. Usually pathogenic, they have been reported to account for up to 27% of the overall BRCA1 and 5% of BRCA2 disease-causing mutations  with a strong founder effect accounting for about 1/3rd of all disease diagnosis. Accurate detection of a BRCA1 or BRCA2 pathogenic variant has immense impact on clinical management of disease including patient’s eligibility for new PARP inhibitors.
LGC Clinical Diagnostics has developed BRCA Reference Materials which include 10 variants in BRCA1 and 10 variants in BRCA2 ranging in size from SNVs to insertions and/or deletions over 500 bp (11 exon-level large rearrangements), resulting in a variety of phenotypic alterations at the amino acid level, including missense, nonsense, frameshift, stop-gain/loss, splice-site, and insertion/deletion of partial or up to two exons (see Product Sheet MKT-00818 for more details).
FEATURES AND BENEFITS
•Develop, monitor, validate and challenge your hybrid capture-based targeted NGS assays with confidence using a highly multiplexed reference material containing biomarkers important in BRCA-driven cancers.
• Single sample with 20 pathogenic BRCA1/2 variants (11 LGRs, 9 deletions, 5 SNVs, 4 indels, and 2 insertions).
• Mutation targets quantitated by highly sensitive dPCR assays, and orthogonally analyzed by NGS.
• All mutations are blended against the well-characterized GM24385 human genomic DNA as ‘wildtype’ background material.
• Available as full process (FFPE curl) or purified genomic DNA at various allele frequencies suited for either somatic or germline testing.
•Manufactured in GMP-compliant and ISO 13485-certified facilities.
1. Wallace AJ. New challenges for BRCA testing: a view from the diagnostic laboratory. Eur J Hum Genet. 2016 Sep;24 Suppl 1(Suppl 1):S10-8. doi: 10.1038/ejhg.2016.94. PMID: 27514839; PMCID: PMC5141576. 2. James PA, Sawyer S, Boyle S, Young MA, Kovalenko S, Doherty R, McKinley J, Alsop K, Beshay V, Harris M, Fox S, Lindeman GJ, Mitchell G. Large genomic rearrangements in the familial breast and ovarian cancer gene BRCA1 are associated with an increased frequency of high risk features. Fam Cancer. 2015 Jun;14(2):287-95. doi: 10.1007/s10689-015-9785-0. PMID: 25678442.