PTEN genetic testing

PTEN genetic testing should be considered in individuals:^r

• who meet revised PTEN hamartoma tumour syndrome (PHTS) clinical diagnostic criteria^r*
• where a known pathogenic mutation is identified in a relative 
• who have a relative who meets revised PTEN hamartoma tumour syndrome clinical diagnostic criteria for whom testing has not been performed AND

i) any two major criteria; OR 
ii) one major and two minor criteria; OR 
iii) three minor criteria^r

The decision to offer a genetic test should be based on the pre-test probability of identifying a heritable mutation, the performance of the test (e.g. false negative rate) and the patient's choice.

*Additional clinical judgement may be necessary when applying these criteria to paediatric and early adult patients, where features necessary to meet diagnostic criteria may not yet all be present.^r For paediatric cases, consider using the Cleveland Clinic PTEN paediatric clinical criteria for testing.^r

The results of the following investigations may significantly influence the likelihood of detecting a heritable mutation in the PTEN gene:

• consideration of the operational criteria for PHTS^r
• clinical examination for the detection of macrocephaly
• clinical examination/biopsy for detection of dermatologic features especially trichilemmomas and oral papillomas.

The true frequency of clinical features in individuals with a PTEN mutation is currently not known.^r

The rate of mutations that arise de novo rather than being inherited is unknown.

Heritable PTEN mutations are estimated to affect about 1 in 200 000 individuals, although this may be an underestimate given the difficulty in diagnosis presented by this highly variable disease and the fact that many component features in and of themselves can occur in the general population.^r

Predictive testing should never be ordered when only a variant of unknown significance or a benign/likely benign variant has been identified in a family.

A range of testing methodologies are needed to identify pathogenic changes in the PTEN gene including:

• sequencing
• MLPA copy number analysis

Information about DNA tests and testing laboratories is available from:

• RCPA catalogue of genetic tests and laboratories
• GeneReviews
• European Directory of DNA Diagnostic Laboratories
• Genetic Testing Registry
• UK Genetic Testing Network

If a decision is made to test this gene(s) 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 is uninformative, the value of testing using another methodology (e.g. MLPA, Sanger sequencing) should be considered.

If a mutation is identified refer to a clinical genetics service or familial cancer centre for review, family risk notification and predictive testing.

If a mosaic mutation is identified refer to a clinical genetics service or familial cancer centre for review and guidance about the penetrance of phenotypic features (including cancer risk).

Link to Pre test counselling information.

The European Molecular Genetics Quality Network

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