Opportunistic Genetic Screening Increases the Diagnostic Yield and is Medically Valuable for Care of Patients and Their Relatives with Hereditary Cancer

Overview

Journal J Med Genet

Specialty Genetics

Date 2023 Aug 17

PMID 37591735

Authors

Sara Fernandez-Castillejo

Barbara Roig

Mireia Mele

Sara Serrano

Monica Salvat

Montserrat Querol

Joan Brunet

Marta Pineda

Adela Cisneros

David Parada

Joan Badia

Joan Borras

Marta Rodriguez-Balada

Josep Guma

Affiliations

Soon will be listed here.

Abstract

Background: Multigene panel testing by next-generation sequencing (MGP-NGS) enables the detection of germline pathogenic or likely pathogenic variants (PVs/LPVs) in genes beyond those associated with a certain cancer phenotype. Opportunistic genetic screening based on MGP-NGS in patients with suspicion of hereditary cancer reveals these incidental findings (IFs).

Methods: MGP-NGS was performed in patients who fulfilled the clinical criteria to undergo genetic testing according to the Catalan Health Service guidelines. Variants were classified following the American College of Medical Genetics and Genomics-Association for Molecular Pathology guidelines and the Cancer Variant Interpretation Group UK guidelines.

Results: IFs were identified in 10 (1.22%) of the 817 patients who underwent MGP-NGS. The mean age at cancer diagnosis was 49.4±9.5 years. Three IFs (30.0%) were detected in , two (20.0%) in and and one (10.0%) in and . Seven (70.0%) IFs were single-nucleotide substitutions, two (20.0%) were deletions and one (10.0%) was a duplication. Three (30.0) IFs were located in intronic regions, three (30.3%) were nonsense, two (20.0%) were frameshift and two (20.0%) were missense variations. Six (60.0%) IFs were classified as PVs and four (40.0%) as LPVs.

Conclusions: Opportunistic genetic screening increased the diagnostic yield by 1.22% in our cohort. Most of the identified IFs were present in clinically actionable genes (n=7; 70.0%), providing these families with an opportunity to join cancer early detection programmes, as well as secondary cancer prevention. IFs might facilitate the diagnosis of asymptomatic individuals and the early management of cancer once it develops.

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