A range of testing methodologies are needed to identify pathogenic changes in the TP53 gene including:
- MLPA copy number analysis
Information about DNA tests and testing laboratories is available from:
When testing for Li-Fraumeni syndrome in someone with a personal history of haematological malignancy, DNA from peripheral blood should not be used, as somatic TP53 pathogenic variant cannot be differentiated from germline pathogenic variant using white blood cell DNA (this includes patients in clinical remission). Similarly, saliva specimens can be contaminated with white blood cells and are not accurate for diagnosis of germline pathogenic variant. Cultured skin fibroblasts from a skin punch biopsy, or DNA extracted from hair bulbs, are the preferred tissue specimens for germline testing.r
If a decision is made to test this gene 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 this gene is tested using genomic sequencing (“next generation sequencing” or NGS), and testing has not identified 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 or skin is uninformative, testing of two or more different tumour samples may be indicated to assess for mosaicism.