Four evolutionary trajectories underlie genetic intratumoral variation in childhood cancer

Jenny Karlsson, Anders Valind, Linda Holmquist Mengelbier, Sofia Bredin, Louise Cornmark, Caroline Jansson, Amina Wali, Johan Staaf, Björn Viklund, Ingrid Øra, Anna Börjesson, Torbjörn Backman, Noémie Braekeveldt, Bengt Sandstedt, Niklas Pal, Anders Isaksson, Barbara Gürtl Lackner, Tord Jonson, Daniel Bexell, David Gisselsson

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)944-950
JournalNature Genetics
Volume50
Issue number7
Early online date2018 Jun 4
DOIs
Publication statusPublished - 2018 Jul

Subject classification (UKÄ)

  • Medical Genetics
  • Cancer and Oncology

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