Which individuals undergoing BRACAnalysis need BART testing?

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Deleterious mutations in BRCA1 and BRCA2 genes include both sequence variants and large genomic rearrangements (LGR).
• Myriad Genetics Laboratory (MGL) has established criteria for ordering LGR testing (BRACAnalysis Rearrangement Test, BART™) alongside BRCA1/BRCA2 testing.

Purpose of the Study:

• To evaluate the proportion of patients with LGR mutations in BRCA1 and BRCA2 who met MGL's established criteria for LGR testing.
• To assess the utility of MGL criteria in identifying patients with LGR mutations.

Main Methods:

• Retrospective chart review of individuals undergoing genetic testing at the institution from August 2006 to August 2009.
• Classification of individuals based on the presence or absence of LGR mutations in BRCA1 or BRCA2.
• Categorization of patient histories according to MGL defined LGR criteria, criteria including third-degree relatives, or no defined criteria.

Main Results:

• A total of 257 BART tests were performed.
• Five individuals (1.9%) were found to have LGR mutations.
• Two LGRs were identified in patients meeting MGL criteria, one in a patient meeting criteria with third-degree relatives, and two in patients not meeting MGL criteria.

Conclusions:

• Large genomic rearrangements (LGR) in BRCA1 and BRCA2 can occur in individuals who do not meet standard pretest probability criteria for mutation.
• These findings support the recommendation for routine inclusion of LGR testing with all BRCA1 and BRCA2 genetic tests.
• Comprehensive LGR testing ensures the most complete and reliable genetic testing results for patients.