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Genome sequencing of normal cells reveals developmental lineages and mutational processes.
Behjati, Sam; Huch, Meritxell; van Boxtel, Ruben; Karthaus, Wouter; Wedge, David C; Tamuri, Asif U; Martincorena, Inigo; Petljak, Mia; Alexandrov, Ludmil B; Gundem, Gunes; Tarpey, Patrick S; Roerink, Sophie; Blokker, Joyce; Maddison, Mark; Mudie, Laura; Robinson, Ben; Nik-Zainal, Serena; Campbell, Peter; Goldman, Nick; van de Wetering, Marc; Cuppen, Edwin; Clevers, Hans; Stratton, Michael R.
Afiliación
  • Behjati S; Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
  • Huch M; Department of Paediatrics, University of Cambridge, Hills Road, Cambridge, CB2 2XY, UK.
  • van Boxtel R; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, CancerGenomiCs.nl & University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands.
  • Karthaus W; Present address: Wellcome Trust / Cancer Research UK Gurdon Institute, Tennis Court Road, CB2 1QN, Cambridge, UK.
  • Wedge DC; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, CancerGenomiCs.nl & University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands.
  • Tamuri AU; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, CancerGenomiCs.nl & University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands.
  • Martincorena I; Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
  • Petljak M; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
  • Alexandrov LB; Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
  • Gundem G; Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
  • Tarpey PS; Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
  • Roerink S; Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
  • Blokker J; Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
  • Maddison M; Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
  • Mudie L; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, CancerGenomiCs.nl & University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands.
  • Robinson B; Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
  • Nik-Zainal S; Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
  • Campbell P; Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
  • Goldman N; Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
  • van de Wetering M; East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK.
  • Cuppen E; Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
  • Clevers H; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
  • Stratton MR; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, CancerGenomiCs.nl & University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands.
Nature ; 513(7518): 422-425, 2014 Sep 18.
Article en En | MEDLINE | ID: mdl-25043003
The somatic mutations present in the genome of a cell accumulate over the lifetime of a multicellular organism. These mutations can provide insights into the developmental lineage tree, the number of divisions that each cell has undergone and the mutational processes that have been operative. Here we describe whole genomes of clonal lines derived from multiple tissues of healthy mice. Using somatic base substitutions, we reconstructed the early cell divisions of each animal, demonstrating the contributions of embryonic cells to adult tissues. Differences were observed between tissues in the numbers and types of mutations accumulated by each cell, which likely reflect differences in the number of cell divisions they have undergone and varying contributions of different mutational processes. If somatic mutation rates are similar to those in mice, the results indicate that precise insights into development and mutagenesis of normal human cells will be possible.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mutagénesis / Genoma / Células Clonales / Linaje de la Célula / Mutación Límite: Animals / Humans / Male Idioma: En Revista: Nature Año: 2014 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mutagénesis / Genoma / Células Clonales / Linaje de la Célula / Mutación Límite: Animals / Humans / Male Idioma: En Revista: Nature Año: 2014 Tipo del documento: Article Pais de publicación: Reino Unido