Germline structural variant as the cause of Lynch Syndrome in a family from Ecuador
Colorectal cancer (CRC) is one of the most common cancers worldwide. Lynch Syndrome (LS) is the most common form of hereditary CRC and it is caused by germline defects in the DNA-mismatch repair (MMR) pathway. It is of extreme importance for affected LS patients and their relatives to identify the germline causative alteration to provide intensified surveillance to those at risk and allow early diagnosis and cancer prevention. Current approaches for LS molecular diagnosis typically involve screening of the MMR genes by targeted gene-panel sequencing and rearrangement screening. We report the identification and characterization of a novel germline structural variant encompassing 48.757 kb, involving the 3'-ends of the MLH1 and LRRFIP2 genes, as the cause of LS in a family of Ecuador. Whole-genome sequencing and transcriptomics allowed the identification of the genomic rearrangement and highlights the importance of the use of these additional approaches to achieve a comprehensive molecular diagnosis in some LS patients.
Authors
- Jenifer Muñoz (ORCID: https://orcid.org/0000-0001-9412-022X)
- Míriam Cuatrecasas (ORCID: https://orcid.org/0000-0003-3063-0110)
- María Isabel Álvarez‐Mora (ORCID: https://orcid.org/0000-0003-3788-8915)
- Anna Esteve‐Codina (ORCID: https://orcid.org/0000-0003-0361-2873)
- Gemma Llargués‐Sistac (ORCID: https://orcid.org/0000-0002-0658-2115)
- Sandra López‐Prades (ORCID: https://orcid.org/0000-0001-8208-2959)
- Sergi Castellvı́-Bel (ORCID: https://orcid.org/0000-0003-1217-5097)
- Francesc Balaguer (ORCID: https://orcid.org/0000-0002-0206-0539)
- Carlos Reyes-Silva
- Antoni Castells (ORCID: https://orcid.org/0000-0001-8431-2033)
- Leticia Moreira (ORCID: https://orcid.org/0000-0002-4518-8591)
- Laia Bonjoch (ORCID: https://orcid.org/0000-0002-3351-0037)
- Guerau Fernández (ORCID: https://orcid.org/0000-0003-2987-9971)
- Célia Bádenas (ORCID: https://orcid.org/0000-0002-0621-0477)
- Gabriela Jaramillo-Koupermann (ORCID: https://orcid.org/0000-0001-8068-1763)
- Xavier Domínguez‐Rovira (ORCID: https://orcid.org/0009-0000-1398-1176)
- Maria Teresa Rodrigo‐Calvo (ORCID: https://orcid.org/0000-0001-6675-3425)
- Teresa Ocaña
Institutions
- Hospital Sant Joan de Déu Barcelona (ES)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Centro de Investigación Biomédica en Red (ES)
- Sant Joan de Déu Research Foundation (ES)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES)
- Centro Nacional de Análisis Genómico (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- npj Genomic Medicine
- Published
- 2025-01-16
- DOI
- https://doi.org/10.1038/s41525-025-00462-y
- Primary Topic
- Genetic factors in colorectal cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fundació la Marató de TV3
- “la Caixa” Foundation
- Centres de Recerca de Catalunya
- European Cooperation in Science and Technology
- Fundación Científica Asociación Española Contra el Cáncer
- Generalitat de Catalunya
- Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya
- Universitat de Barcelona
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
- Horizon 2020 Framework Programme
- HORIZON EUROPE Framework Programme
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Instituto de Salud Carlos III