Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer.
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| 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.
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| Authors | 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 |
| Journal | Nature communications (Nat Commun) Vol. 6 Pg. 6125 (Jan 27 2015) ISSN: 2041-1723 [Electronic] England |
| PMID | 25625758 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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