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Four evolutionary trajectories underlie genetic intratumoral variation in childhood cancer

Karlsson, Jenny LU ; Valind, Anders LU ; Holmquist Mengelbier, Linda LU ; Bredin, Sofia; Cornmark, Louise LU ; Jansson, Caroline LU ; Wali, Amina; Staaf, Johan LU ; Viklund, Björn and Øra, Ingrid LU , et al. (2018) In Nature Genetics p.1-7
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,... (More)

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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@article{c77811db-2162-4b32-8c67-569b355ae62b,
  abstract     = {<p>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 unexplored<sup>1–5</sup>. 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.</p>},
  author       = {Karlsson, Jenny and Valind, Anders and Holmquist Mengelbier, Linda and Bredin, Sofia and Cornmark, Louise and Jansson, Caroline and Wali, Amina and Staaf, Johan and Viklund, Björn and Øra, Ingrid and Börjesson, Anna and Backman, Torbjörn and Braekeveldt, Noémie and Sandstedt, Bengt and Pal, Niklas and Isaksson, Anders and Lackner, Barbara Gürtl and Jonson, Tord and Bexell, Daniel and Gisselsson, David},
  issn         = {1061-4036},
  language     = {eng},
  month        = {06},
  pages        = {1--7},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Four evolutionary trajectories underlie genetic intratumoral variation in childhood cancer},
  url          = {http://dx.doi.org/10.1038/s41588-018-0131-y},
  year         = {2018},
}