A range of testing methodologies are needed to identify pathogenic changes in the BRCA 1, BRCA 2 or PALB2 genes including:
- sequencing
- copy number analysis.
Information about DNA tests and testing laboratories is available from:
Where possible, BRCA1, BRCA2 and PALB2 testing should be done as part of a panel test (refer to Breast cancer – panel testing, Ovarian cancer (epithelial) – panel testing, Pancreatic cancer – panel testing or Prostate cancer – panel testing). Clinical features and/or additional family history may guide choice of additional genes (e.g. CDH1, TP53, PTEN, MMR).
If a decision is made to test these genes as part of a cancer gene panel, care should be taken to select a panel where the individual genes tested have both clinical validity and clinical utility.
A variant-specific test (rather than sequencing a single gene or gene panel) may be more appropriate and cost effective where a relative is known to have a germline pathogenic variant or a pathogenic variant has been identified in the patient’s tumour.
If these genes are tested using genomic sequencing (“next generation sequencing” or NGS), and testing has not identified a pathogenic variant, the value of testing using another methodology should be considered in high risk families.
If genetic testing in DNA from peripheral blood is uninformative, testing of two or more different tumour samples may be indicated to assess for mosaicism.