Your browser doesn't support javascript.
loading
Detection of a major Lynch Syndrome-causing MLH1 founder variant in a large-scale genotyped cohort.
Sipilä, Lauri J; Aavikko, Mervi; Ravantti, Janne; Martin, Samantha; Kuopio, Teijo; Lahtinen, Laura; Peltomäki, Päivi; Mecklin, Jukka-Pekka; Aaltonen, Lauri A; Seppälä, Toni T.
Afiliación
  • Sipilä LJ; Department of Medical and Clinical Genetics, University of Helsinki, Biomedicum Helsinki Haartmaninkatu 8), PO Box 63, 00014, Helsinki, Finland.
  • Aavikko M; Applied Tumor Genomics, Research Programs Unit, University of Helsinki, Biomedicum Helsinki Haartmaninkatu 8), PO Box 63, 00014, Helsinki, Finland.
  • Ravantti J; Finnish Cancer Registry, Unioninkatu 22, 00130, Helsinki, Finland.
  • Martin S; Department of Medical and Clinical Genetics, University of Helsinki, Biomedicum Helsinki Haartmaninkatu 8), PO Box 63, 00014, Helsinki, Finland.
  • Kuopio T; Applied Tumor Genomics, Research Programs Unit, University of Helsinki, Biomedicum Helsinki Haartmaninkatu 8), PO Box 63, 00014, Helsinki, Finland.
  • Lahtinen L; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
  • FinnGen; Department of Medical and Clinical Genetics, University of Helsinki, Biomedicum Helsinki Haartmaninkatu 8), PO Box 63, 00014, Helsinki, Finland.
  • Peltomäki P; Applied Tumor Genomics, Research Programs Unit, University of Helsinki, Biomedicum Helsinki Haartmaninkatu 8), PO Box 63, 00014, Helsinki, Finland.
  • Mecklin JP; Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, FI-00014, Helsinki, Finland.
  • Aaltonen LA; Department of Medical and Clinical Genetics, University of Helsinki, Biomedicum Helsinki Haartmaninkatu 8), PO Box 63, 00014, Helsinki, Finland.
  • Seppälä TT; Applied Tumor Genomics, Research Programs Unit, University of Helsinki, Biomedicum Helsinki Haartmaninkatu 8), PO Box 63, 00014, Helsinki, Finland.
Fam Cancer ; 23(4): 647-652, 2024 Nov.
Article en En | MEDLINE | ID: mdl-38847920
ABSTRACT
Some 50% of Finnish Lynch Syndrome (LS) cases are caused by a founder variant in MLH1, in which the entire exon 16 has been lost due to an Alu-mediated recombination event. We piloted detecting the variant in FinnGen, a large genotyped cohort comprising approximately 10% of the current Finnish population, and validated the MLH1 founder variant status of identified individuals residing in the Central Finland Biobank catchment area. A consensus sequence flanking the deletion was identified in whole genome sequences of six LS individuals with the founder variant. Genotype data of 212,196 individuals was queried for regional matches to the consensus sequence. Enrichment of cancer and age at cancer onset was compared between matching and non-matching individuals. Variant status was validated for a subset of the identified individuals using a polymerase chain reaction assay. Allelic matches in a chosen target region was detected in 348 individuals, with 89 having a cancer diagnosis (Bonferroni-adjusted p-value = 1), 20 a familial cancer history (p-adj. < .001), with mean age of onset of cancer being 53.6 years (p-adj. = .002). Eighteen of potential variant carriers had been sampled by the Central Finland Biobank, of which four (22%) were validated as true variant carriers. The workflow we have employed identifies MLH1 exon 16 deletion variant carriers from population-wide SNP genotyping data. An alternative design will be sought to limit false positive findings. Large genotyped cohorts provide a potential resource for identification and prevention of hereditary cancer.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales Hereditarias sin Poliposis / Homólogo 1 de la Proteína MutL / Genotipo Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Fam Cancer Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales Hereditarias sin Poliposis / Homólogo 1 de la Proteína MutL / Genotipo Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Fam Cancer Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Países Bajos