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Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer.

Holmquist Mengelbier, Linda LU ; Karlsson, Jenny LU ; Lindgren, David LU ; Valind, Anders LU ; Lilljebjörn, Henrik LU ; Jansson, Caroline LU ; Bexell, Daniel LU ; Braekeveldt, Noémie LU ; Ameur, Adam and Jonson, Tord LU , et al. (2015) In Nature Communications 6.
Abstract
Genetic differences among neoplastic cells within the same tumour have been proposed to drive cancer progression and treatment failure. Whether data on intratumoral diversity can be used to predict clinical outcome remains unclear. We here address this issue by quantifying genetic intratumoral diversity in a set of chemotherapy-treated childhood tumours. By analysis of multiple tumour samples from seven patients we demonstrate intratumoral diversity in all patients analysed after chemotherapy, typically presenting as multiple clones within a single millimetre-sized tumour sample (microdiversity). We show that microdiversity often acts as the foundation for further genome evolution in metastases. In addition, we find that microdiversity... (More)
Genetic differences among neoplastic cells within the same tumour have been proposed to drive cancer progression and treatment failure. Whether data on intratumoral diversity can be used to predict clinical outcome remains unclear. We here address this issue by quantifying genetic intratumoral diversity in a set of chemotherapy-treated childhood tumours. By analysis of multiple tumour samples from seven patients we demonstrate intratumoral diversity in all patients analysed after chemotherapy, typically presenting as multiple clones within a single millimetre-sized tumour sample (microdiversity). We show that microdiversity often acts as the foundation for further genome evolution in metastases. In addition, we find that microdiversity predicts poor cancer-specific survival (60%; P=0.009), independent of other risk factors, in a cohort of 44 patients with chemotherapy-treated childhood kidney cancer. Survival was 100% for patients lacking microdiversity. Thus, intratumoral genetic diversity is common in childhood cancers after chemotherapy and may be an important factor behind treatment failure. (Less)
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Nature Communications
volume
6
publisher
Nature Publishing Group
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  • pmid:25625758
  • wos:000348832000001
  • scopus:84923088262
ISSN
2041-1723
DOI
10.1038/ncomms7125
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English
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yes
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a271e410-8ca0-408b-85f3-cba2b91fd074 (old id 5039438)
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http://www.ncbi.nlm.nih.gov/pubmed/25625758?dopt=Abstract
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2015-02-04 18:19:48
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@article{a271e410-8ca0-408b-85f3-cba2b91fd074,
  abstract     = {Genetic differences among neoplastic cells within the same tumour have been proposed to drive cancer progression and treatment failure. Whether data on intratumoral diversity can be used to predict clinical outcome remains unclear. We here address this issue by quantifying genetic intratumoral diversity in a set of chemotherapy-treated childhood tumours. By analysis of multiple tumour samples from seven patients we demonstrate intratumoral diversity in all patients analysed after chemotherapy, typically presenting as multiple clones within a single millimetre-sized tumour sample (microdiversity). We show that microdiversity often acts as the foundation for further genome evolution in metastases. In addition, we find that microdiversity predicts poor cancer-specific survival (60%; P=0.009), independent of other risk factors, in a cohort of 44 patients with chemotherapy-treated childhood kidney cancer. Survival was 100% for patients lacking microdiversity. Thus, intratumoral genetic diversity is common in childhood cancers after chemotherapy and may be an important factor behind treatment failure.},
  articleno    = {6125},
  author       = {Holmquist Mengelbier, Linda and Karlsson, Jenny and Lindgren, David and Valind, Anders and Lilljebjörn, Henrik and Jansson, Caroline and Bexell, Daniel and Braekeveldt, Noémie and Ameur, Adam and Jonson, Tord and Kultima, Hanna Göransson and Isaksson, Anders and Asmundsson, Jurate and Versteeg, Rogier and Rissler, Marianne and Fioretos, Thoas and Sandstedt, Bengt and Börjesson, Anna and Backman, Torbjörn and Pal, Niklas and Øra, Ingrid and Mayrhofer, Markus and Gisselsson Nord, David},
  issn         = {2041-1723},
  language     = {eng},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer.},
  url          = {http://dx.doi.org/10.1038/ncomms7125},
  volume       = {6},
  year         = {2015},
}