Germline Cancer Susceptibility Gene Testing in Unselected Patients with Hepatobiliary Cancers: A Multi-Center...

Area of Science:

• Oncology
• Genetics
• Cancer Research

Background:

• Limited data exists on germline testing in unselected hepatobiliary cancer patients.
• Identifying germline predisposition is crucial for cancer treatment and family genetic counseling.

Purpose of the Study:

• To determine the prevalence of pathogenic germline variants (PGVs) in patients with hepatobiliary cancers.
• To assess the implications of universal multi-gene panel testing for treatment and counseling.

Main Methods:

• Prospective multi-site study involving germline sequencing of >80 genes.
• Analysis of 205 unselected patients with hepatobiliary cancers between April 2018 and March 2020.
• Offered family cascade testing at no cost.

Main Results:

• Pathogenic germline variants (PGVs) were found in 15.6% of patients, with 71% in moderate/high penetrance genes.
• 75% of patients with positive results would not have been identified by current genetic evaluation guidelines.
• Prevalence varied by cancer type, reaching 33% in carcinoma of the ampulla of Vater.
• 55% of patients were potentially eligible for precision therapy or clinical trials.

Conclusions:

• Universal multi-gene panel testing detects heritable mutations in over 15% of hepatobiliary cancer patients.
• Current guidelines miss a significant proportion of patients with actionable germline mutations.
• Germline testing should be considered for all patients diagnosed with hepatobiliary cancers.