A range of testing methodologies is needed to identify pathogenic changes in the MMR genes including:
- copy number analysis (e.g. MLPA, including EPCAM gene)
- methylation analysis
- analysis for structural rearrangements (e.g. MSH2 inversion)
- testing of the PMS2 gene, which can be difficult due to the presence of pseudogenes. Consideration should be given to long range PCR of the whole gene if a pathogenic variant is not found with conventional testing.
Information about DNA tests and testing laboratories is available from:
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.
If these genes are tested using genomic sequencing (“next generation sequencing” or NGS), and testing does not identify a pathogenic variant, the value of testing using another methodology (e.g. MLPA, Sanger sequencing) should be considered.
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.