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Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer

Author

Listed:
  • Linda Holmquist Mengelbier

    (Lund University)

  • Jenny Karlsson

    (Lund University)

  • David Lindgren

    (Translational Cancer Research, Lund University)

  • Anders Valind

    (Lund University)

  • Henrik Lilljebjörn

    (Lund University)

  • Caroline Jansson

    (Lund University)

  • Daniel Bexell

    (Translational Cancer Research, Lund University)

  • Noémie Braekeveldt

    (Translational Cancer Research, Lund University)

  • Adam Ameur

    (Genetics and Pathology, Science for Life Laboratory, Uppsala University)

  • Tord Jonson

    (Lund University)

  • Hanna Göransson Kultima

    (Array and Analysis Facility, Uppsala University)

  • Anders Isaksson

    (Array and Analysis Facility, Uppsala University)

  • Jurate Asmundsson

    (Karolinska University Hospital)

  • Rogier Versteeg

    (Academic Medical Center)

  • Marianne Rissler

    (Lund University)

  • Thoas Fioretos

    (Lund University)

  • Bengt Sandstedt

    (Karolinska Institute)

  • Anna Börjesson

    (Lund University, University Hospital)

  • Torbjörn Backman

    (Lund University, University Hospital)

  • Niklas Pal

    (Astrid Lindgren Children’s Hospital, Karolinska University Hospital)

  • Ingrid Øra

    (Lund University, University Hospital)

  • Markus Mayrhofer

    (Array and Analysis Facility, Uppsala University)

  • David Gisselsson

    (Lund University
    Skåne Regional and University Laboratories)

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.

Suggested Citation

  • Linda Holmquist Mengelbier & Jenny Karlsson & David Lindgren & Anders Valind & Henrik Lilljebjörn & Caroline Jansson & Daniel Bexell & Noémie Braekeveldt & Adam Ameur & Tord Jonson & Hanna Göransson K, 2015. "Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer," Nature Communications, Nature, vol. 6(1), pages 1-10, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7125
    DOI: 10.1038/ncomms7125
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    Cited by:

    1. Jenny Karlsson & Hiroaki Yasui & Adriana Mañas & Natalie Andersson & Karin Hansson & Kristina Aaltonen & Caroline Jansson & Geoffroy Durand & Naveen Ravi & Michele Ferro & Minjun Yang & Subhayan Chatt, 2024. "Early evolutionary branching across spatial domains predisposes to clonal replacement under chemotherapy in neuroblastoma," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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