Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer

Linda Holmquist Mengelbier; Jenny Karlsson; David Lindgren; Anders Valind; Henrik Lilljebjörn; Caroline Jansson; Daniel Bexell; Noémie Braekeveldt; Adam Ameur; Tord Jonson; Hanna Göransson Kultima; Anders Isaksson; Jurate Asmundsson; Rogier Versteeg; Marianne Rissler; Thoas Fioretos; Bengt Sandstedt; Anna Börjesson; Torbjörn Backman; Niklas Pal; Ingrid Øra; Markus Mayrhofer; David Gisselsson

doi:https://doi.org/10.1038/ncomms7125

Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer

Linda Holmquist Mengelbier, Jenny Karlsson, David Lindgren, Anders Valind, Henrik Lilljebjörn, Caroline Jansson, Daniel Bexell, Noémie Braekeveldt, Adam Ameur, Tord Jonson, Hanna Göransson Kultima, Anders Isaksson, Jurate Asmundsson, Rogier Versteeg, Marianne Rissler, Thoas Fioretos, Bengt Sandstedt, Anna Börjesson, Torbjörn Backman, Niklas PalIngrid Øra, Markus Mayrhofer, David Gisselsson

Research output: Contribution to journal › Article › Academic › peer-review

52 Citations (Scopus)

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

Original language	English
Pages (from-to)	6125
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7125
Publication status	Published - 2015

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https://doi.org/10.1038/ncomms7125

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Mengelbier, L. H., Karlsson, J., Lindgren, D., Valind, A., Lilljebjörn, H., Jansson, C., Bexell, D., Braekeveldt, N., Ameur, A., Jonson, T., Kultima, H. G., Isaksson, A., Asmundsson, J., Versteeg, R., Rissler, M., Fioretos, T., Sandstedt, B., Börjesson, A., Backman, T., ... Gisselsson, D. (2015). Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer. Nature communications, 6, 6125. https://doi.org/10.1038/ncomms7125

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title = "Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer",

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",

author = "Mengelbier, {Linda Holmquist} and Jenny Karlsson and David Lindgren and Anders Valind and Henrik Lilljebj{\"o}rn and Caroline Jansson and Daniel Bexell and No{\'e}mie Braekeveldt and Adam Ameur and Tord Jonson and Kultima, {Hanna G{\"o}ransson} and Anders Isaksson and Jurate Asmundsson and Rogier Versteeg and Marianne Rissler and Thoas Fioretos and Bengt Sandstedt and Anna B{\"o}rjesson and Torbj{\"o}rn Backman and Niklas Pal and Ingrid {\O}ra and Markus Mayrhofer and David Gisselsson",

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doi = "https://doi.org/10.1038/ncomms7125",

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Mengelbier, LH, Karlsson, J, Lindgren, D, Valind, A, Lilljebjörn, H, Jansson, C, Bexell, D, Braekeveldt, N, Ameur, A, Jonson, T, Kultima, HG, Isaksson, A, Asmundsson, J, Versteeg, R, Rissler, M, Fioretos, T, Sandstedt, B, Börjesson, A, Backman, T, Pal, N, Øra, I, Mayrhofer, M & Gisselsson, D 2015, 'Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer', Nature communications, vol. 6, pp. 6125. https://doi.org/10.1038/ncomms7125

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AU - Mengelbier, Linda Holmquist

AU - Karlsson, Jenny

AU - Lindgren, David

AU - Valind, Anders

AU - Lilljebjörn, Henrik

AU - Jansson, Caroline

AU - Bexell, Daniel

AU - Braekeveldt, Noémie

AU - Ameur, Adam

AU - Jonson, Tord

AU - Kultima, Hanna Göransson

AU - Isaksson, Anders

AU - Asmundsson, Jurate

AU - Versteeg, Rogier

AU - Rissler, Marianne

AU - Fioretos, Thoas

AU - Sandstedt, Bengt

AU - Börjesson, Anna

AU - Backman, Torbjörn

AU - Pal, Niklas

AU - Øra, Ingrid

AU - Mayrhofer, Markus

AU - Gisselsson, David

PY - 2015

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N2 - 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

AB - 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

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