Germline structural variant as the cause of Lynch Syndrome in a family from Ecuador
Por:
Llargués-Sistac G, Bonjoch L, Muñoz J, Domínguez-Rovira X, Ocaña T, Alvarez-Mora MI, Badenas C, Esteve-Codina A, Reyes-Silva C, Jaramillo-Koupermann G, Rodrigo MT, López-Prades S, Cuatrecasas M, Castells A, Balaguer F, Moreira L, Fernandez-Isern G and Castellví-Bel S
Publicada:
17 ene 2025
Ahead of Print:
17 ene 2025
Resumen:
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.
Filiaciones:
Llargués-Sistac G:
Gastroenterology Deparment, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
Bonjoch L:
Gastroenterology Deparment, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
Muñoz J:
Gastroenterology Deparment, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
Domínguez-Rovira X:
Gastroenterology Deparment, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
Ocaña T:
Gastroenterology Deparment, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
Alvarez-Mora MI:
Biochemistry and Molecular Genetics Department, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red en Enfermedades Raras (CIBERER), Barcelona, Spain
Badenas C:
Biochemistry and Molecular Genetics Department, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red en Enfermedades Raras (CIBERER), Barcelona, Spain
Esteve-Codina A:
Centro Nacional de Análisis Genómico (CNAG), University of Barcelona, Barcelona, Spain
Reyes-Silva C:
Hospital de Especialidades Eugenio Espejo, Quito, Ecuador
Jaramillo-Koupermann G:
Hospital de Especialidades Eugenio Espejo, Quito, Ecuador
Rodrigo MT:
Pathology Department, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
López-Prades S:
Pathology Department, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
Cuatrecasas M:
Pathology Department, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
Castells A:
Gastroenterology Deparment, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
Balaguer F:
Gastroenterology Deparment, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
Moreira L:
Gastroenterology Deparment, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
Fernandez-Isern G:
Genetic and Molecular Medicine-IPER Department, Hospital Sant Joan de Déu, Institut de Recerca Hospital Sant Joan de Déu, Centro de Investigacion Biomedica en Red en Enfermedades Raras (CIBERER), 08950 Esplugues de Llobregat, Barcelona, Spain
Castellví-Bel S:
Gastroenterology Deparment, Hospital Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
Univ Barcelona, Hosp Clin Barcelona,Gastroenterol Dept, Inst Invest
Biomed August Pi Sunyer IDIBAPS i, Ctr Invest Biomed Red Enfermedades
Hepat & Digest, Barcelona, Spain
Hosp Clin Barcelona, Inst Invest Biomed August Pi Sunyer IDIBAPS i, Ctr
Invest Biomed Red Enfermedades Raras CIBERER, Biochem & Mol Genet Dept,
Barcelona, Spain
Univ Barcelona, Ctr Nacl Anal Genomico CNAG, Barcelona, Spain
Hosp Especial Eugenio Espejo, Quito, Ecuador
Invest Biomed Red Enfermedades Hepat & Digest, Pathol Dept, Barcelona,
Spain
Hosp St Joan Deu, Inst Recerca Hosp Sant Joan Deu, Ctr Invest Biomed Red
Enfermedades Raras CIBERER, Genet & Mol Med IPER Dept, Esplugas de
Llobregat 08950, Barcelona, Spain
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