Tumor Testing and Genetic Analysis to Identify Lynch Syndrome Patients in an Italian Colorectal Cancer Cohort

Lynch syndrome (LS) is an inherited cancer susceptibility syndrome caused by germline mutations in a DNA mismatch repair (MMR) gene or in the EPCAM gene. LS is associated with an increased lifetime risk of colorectal cancer (CRC) and other malignancies. The screening algorithm for LS patient selecti...

Full description

Saved in:
Bibliographic Details
Published in:Cancers 2023-10, Vol.15 (20), p.5061
Main Authors: Pantaleo, Antonino, Forte, Giovanna, Cariola, Filomena, Valentini, Anna Maria, Fasano, Candida, Sanese, Paola, Grossi, Valentina, Buonadonna, Antonia Lucia, De Marco, Katia, Lepore Signorile, Martina, Guglielmi, Anna Filomena, Manghisi, Andrea, Gigante, Gianluigi, Armentano, Raffaele, Disciglio, Vittoria, Simone, Cristiano
Format: Article
Language:English
Subjects:
Algorithms
Analysis
Cancer
Colorectal cancer
Colorectal carcinoma
Data analysis
DNA repair
Family medical history
Gastroenterology
Genes
Genetic analysis
Genetic counseling
Genetic screening
Genetic testing
Genomics
Health aspects
Malignancy
Medical genetics
Microsatellite instability
Mismatch repair
Mutation
Patients
Pharmacogenetics
Precision medicine
Proteins
Risk factors
Software
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Lynch syndrome (LS) is an inherited cancer susceptibility syndrome caused by germline mutations in a DNA mismatch repair (MMR) gene or in the EPCAM gene. LS is associated with an increased lifetime risk of colorectal cancer (CRC) and other malignancies. The screening algorithm for LS patient selection is based on the identification of CRC specimens that have MMR loss/high microsatellite instability (MSI-H) and are wild-type for BRAFV600. Here, we sought to clinically and molecularly characterize patients with these features. From 2017 to 2023, 841 CRC patients were evaluated for MSI and BRAFV600E mutation status, 100 of which showed MSI-H. Of these, 70 were wild-type for BRAFV600. Among these 70 patients, 30 were genetically tested for germline variants in hereditary cancer predisposition syndrome genes. This analysis showed that 19 of these 30 patients (63.3%) harbored a germline pathogenic or likely pathogenic variant in MMR genes, 2 (6.7%) harbored a variant of unknown significance (VUS) in MMR genes, 3 (10%) harbored a VUS in other cancer-related genes, and 6 (20%) were negative to genetic testing. These findings highlight the importance of personalized medicine for tailored genetic counseling, management, and surveillance of families with LS and other hereditary cancer syndromes.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers15205061