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Mutational landscape of normal epithelial cells in Lynch Syndrome patients.
Lee, Bernard C H; Robinson, Philip S; Coorens, Tim H H; Yan, Helen H N; Olafsson, Sigurgeir; Lee-Six, Henry; Sanders, Mathijs A; Siu, Hoi Cheong; Hewinson, James; Yue, Sarah S K; Tsui, Wai Yin; Chan, Annie S Y; Chan, Anthony K W; Ho, Siu Lun; Campbell, Peter J; Martincorena, Inigo; Buczacki, Simon J A; Yuen, Siu Tsan; Leung, Suet Yi; Stratton, Michael R.
Afiliación
  • Lee BCH; Hereditary Gastrointestinal Cancer Genetic Diagnosis Laboratory, Department of Pathology, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
  • Robinson PS; Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.
  • Coorens THH; Department of Paediatrics, University of Cambridge, Cambridge, CB2 0QQ, UK.
  • Yan HHN; Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.
  • Olafsson S; Hereditary Gastrointestinal Cancer Genetic Diagnosis Laboratory, Department of Pathology, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
  • Lee-Six H; Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.
  • Sanders MA; Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.
  • Siu HC; Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.
  • Hewinson J; Hereditary Gastrointestinal Cancer Genetic Diagnosis Laboratory, Department of Pathology, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
  • Yue SSK; Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.
  • Tsui WY; Hereditary Gastrointestinal Cancer Genetic Diagnosis Laboratory, Department of Pathology, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
  • Chan ASY; Hereditary Gastrointestinal Cancer Genetic Diagnosis Laboratory, Department of Pathology, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
  • Chan AKW; Hereditary Gastrointestinal Cancer Genetic Diagnosis Laboratory, Department of Pathology, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
  • Ho SL; Hereditary Gastrointestinal Cancer Genetic Diagnosis Laboratory, Department of Pathology, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
  • Campbell PJ; Hereditary Gastrointestinal Cancer Genetic Diagnosis Laboratory, Department of Pathology, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
  • Martincorena I; Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.
  • Buczacki SJA; Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.
  • Yuen ST; Nuffield Department of Surgical Sciences, University of Oxford, Headington, Oxford, OX3 7DQ, UK.
  • Leung SY; Hereditary Gastrointestinal Cancer Genetic Diagnosis Laboratory, Department of Pathology, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
  • Stratton MR; Hereditary Gastrointestinal Cancer Genetic Diagnosis Laboratory, Department of Pathology, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong. suetyi@hku.hk.
Nat Commun ; 13(1): 2710, 2022 05 17.
Article en En | MEDLINE | ID: mdl-35581206
Lynch Syndrome (LS) is an autosomal dominant disease conferring a high risk of colorectal cancer due to germline heterozygous mutations in a DNA mismatch repair (MMR) gene. Although cancers in LS patients show elevated somatic mutation burdens, information on mutation rates in normal tissues and understanding of the trajectory from normal to cancer cell is limited. Here we whole genome sequence 152 crypts from normal and neoplastic epithelial tissues from 10 LS patients. In normal tissues the repertoire of mutational processes and mutation rates is similar to that found in wild type individuals. A morphologically normal colonic crypt with an increased mutation burden and MMR deficiency-associated mutational signatures is identified, which may represent a very early stage of LS pathogenesis. Phylogenetic trees of tumour crypts indicate that the most recent ancestor cell of each tumour is already MMR deficient and has experienced multiple cycles of clonal evolution. This study demonstrates the genomic stability of epithelial cells with heterozygous germline MMR gene mutations and highlights important differences in the pathogenesis of LS from other colorectal cancer predisposition syndromes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales Hereditarias sin Poliposis Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Hong Kong Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales Hereditarias sin Poliposis Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Hong Kong Pais de publicación: Reino Unido