Gemelli IRCCS tumor profiling of 2674 patients found hereditary cancer-risk variants in about 10%
Profiling over 500 genes in solid tumors at Gemelli IRCCS revealed constitutional pathogenic variants in about 10% of patients; some fall outside current testing guidelines.
Researchers at Fondazione Policlinico Universitario A. Gemelli IRCCS reported that comprehensive cancer genome profiling of solid tumors detected constitutional pathogenic or likely pathogenic variants in about 10% of an unselected cohort, according to a paper in Genome Medicine doi.org
Genome Medicinedoi.orgOpen source ↗. The analysis covers the first two years of the FPG500 program, from January 2022 to December 2023. It included 2688 samples from 2674 patients, more than half of them with cancers of the female reproductive system
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Genome Medicinedoi.orgOpen source ↗.
The trial is prospective and interventional. Patients with solid tumors who had a clinical indication for molecular testing under national guidelines were referred for profiling. The panel analyzes over 500 genes. According to the investigators, this is not part of standard clinical practice in Italy, where reimbursed tests target a limited number of genes tied to specific cancer types.
Germline testing and confirmation
Variants suspected to be constitutional led to referral for genetic evaluation of 16% of patients, covering 527 suspected variants; 80% of those invited attended genetic counselling doi.org
Genome Medicinedoi.orgOpen source ↗. In total, 331 patients underwent germline testing. Of them, 73% carried at least one pathogenic variant, and 66% of tested variants were confirmed as germline
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Genome Medicinedoi.orgOpen source ↗.
Additional constitutional variants were identified in 0,6% of the entire cohort, based on other somatic tests or on tests requested after genetic counselling doi.org
Genome Medicinedoi.orgOpen source ↗.
Variants outside current guidelines
Among the germline variants, 16% were secondary findings, and 20% of the confirmed variants detected in tumor were in moderate-risk genes doi.org
Genome Medicinedoi.orgOpen source ↗. The authors state that such variants would not have been detected under current guidelines. According to the group, standard diagnostic pathways would likely have missed about one-third of individuals with a hereditary cancer-predisposition syndrome.
The team, coordinated by Maurizio Genuardi, says the information can guide therapeutic decisions, surveillance of other organs at risk, and risk-reduction measures such as prophylactic surgery or targeted medical therapy. It also allows testing of relatives to determine whether they inherited the family variant. The trial is registered at ClinicalTrials.gov as NCT06020625 doi.org
Genome Medicinedoi.orgOpen source ↗.
The researchers plan to study further hereditary alterations in genes beyond those analyzed so far. They also intend to measure how many patients and relatives subsequently entered surveillance and prevention programs.
