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Four evolutionary trajectories underlie genetic intratumoral variation in childhood cancer.
Karlsson, Jenny; Valind, Anders; Holmquist Mengelbier, Linda; Bredin, Sofia; Cornmark, Louise; Jansson, Caroline; Wali, Amina; Staaf, Johan; Viklund, Björn; Øra, Ingrid; Börjesson, Anna; Backman, Torbjörn; Braekeveldt, Noémie; Sandstedt, Bengt; Pal, Niklas; Isaksson, Anders; Lackner, Barbara Gürtl; Jonson, Tord; Bexell, Daniel; Gisselsson, David.
Afiliación
  • Karlsson J; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Valind A; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Holmquist Mengelbier L; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Bredin S; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Cornmark L; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Jansson C; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Wali A; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Staaf J; Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.
  • Viklund B; Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Øra I; Division of Pediatric Oncology, Department of Clinical Sciences, Lund University, Lund, Sweden.
  • Börjesson A; Division of Pediatric Surgery, Department of Clinical Sciences, Lund University, Lund, Sweden.
  • Backman T; Division of Pediatric Surgery, Department of Clinical Sciences, Lund University, Lund, Sweden.
  • Braekeveldt N; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Sandstedt B; Division of Pediatric Oncology and the Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
  • Pal N; Division of Pediatric Oncology and the Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
  • Isaksson A; Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Lackner BG; Department of Pathology, Laboratory Medicine, Medical Services Skåne, Lund, Sweden.
  • Jonson T; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Bexell D; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Gisselsson D; Department of Pathology, Laboratory Medicine, Medical Services Skåne, Lund, Sweden.
Nat Genet ; 50(7): 944-950, 2018 07.
Article en En | MEDLINE | ID: mdl-29867221
A major challenge to personalized oncology is that driver mutations vary among cancer cells inhabiting the same tumor. Whether this reflects principally disparate patterns of Darwinian evolution in different tumor regions has remained unexplored1-5. We mapped the prevalence of genetically distinct clones over 250 regions in 54 childhood cancers. This showed that primary tumors can simultaneously follow up to four evolutionary trajectories over different anatomic areas. The most common pattern consists of subclones with very few mutations confined to a single tumor region. The second most common is a stable coexistence, over vast areas, of clones characterized by changes in chromosome numbers. This is contrasted by a third, less frequent, pattern where a clone with driver mutations or structural chromosome rearrangements emerges through a clonal sweep to dominate an anatomical region. The fourth and rarest pattern is the local emergence of a myriad of clones with TP53 inactivation. Death from disease was limited to tumors exhibiting the two last, most dynamic patterns.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mutación / Neoplasias Tipo de estudio: Risk_factors_studies Límite: Child / Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2018 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mutación / Neoplasias Tipo de estudio: Risk_factors_studies Límite: Child / Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2018 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos