BRCA1 and BRCA2 Deletion/Duplication Analysis
Definition
In these panels, in addition to BRCA1/BRCA2, the TP53, CDH1, PTEN and PALB2 gene regions are screened together; each leads to a separate syndrome that increases hereditary breast cancer risk through a different mechanism. Pathogenic variants in TP53 cause Li-Fraumeni syndrome, in which breast cancer risk appears at an early age and can even exceed that of BRCA carriers. CDH1 variants lead to hereditary diffuse gastric cancer syndrome; women with this syndrome also have a markedly increased risk of lobular-type breast cancer. PTEN variants cause Cowden syndrome (PTEN hamartoma tumor syndrome), increasing breast, thyroid and endometrial cancer risk. PALB2 encodes a partner protein that positions the BRCA2 protein for DNA repair and is itself considered a significant breast cancer risk gene. The panel aims to evaluate these different risk profiles in a single sample. (A separate glossary entry exists for BRCA1/BRCA2 itself.)
Gene/region examined
BRCA1, BRCA2
Method
MLPA Analysis
Accepted sample types
EDTA blood
Description
Deletions and duplications in the BRCA1 and BRCA2 genes are examined.
Inheritance
All five are inherited in an autosomal dominant manner; a pathogenic variant in one copy of the gene is enough to increase risk. In somatic panel versions, the analysis may also cover changes acquired in tumor tissue.