Comprehensive genetic analysis in biliary tract cancer: a prospective single-center experience

Recent data reported a significant incidence of germline aberrations in biliary tract cancer (BTC) patients, even if conclusive data on that and on its clinical implication are lacking.

We selected patients for genetic counselling basing on four criteria: personal history of oncologic disease other than BTC; familial history of oncologic disease (considering relatives of first and second grade); patients ≤50 years old; patients presenting a somatic mutation in genes involved in DNA damage repair pathways and mismatch repair.

A total of 22/150 patients met at least one criterion and were directed to genetic counselling. Of these, 17 received the germline test. Four patients carried a pathogenic variant. Some 18/22 patients received the somatic test on tissue samples. Patients who carried a germline pathogenic variant had the same variant also at a somatic level. No statistically significant differences were found in terms of incidence of germline pathogenic variants between patients diagnosed with BTC before the age of 50 years versus after the age of 50 years and in patients with intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma.

The present study is one of the first prospective experiences investigating the role of genetic counselling and germline testing in a BTC setting, thus suggesting several improvements in the selection criteria of patients directed to genetic counselling.