Menu

Javascript is not activated in your browser. This website needs javascript activated to work properly.
You are here

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

Author:
  • 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 Nord
Publishing year: 2015
Language: English
Publication/Series: Nature Communications
Volume: 6
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

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.

Keywords

  • Cancer and Oncology
  • Medical Genetics
  • Pediatrics

Other

Published
  • Pathways of cancer cell evolution
  • Molecular Pediatric Oncology
  • ISSN: 2041-1723
Thoas Fioretos
E-mail: thoas [dot] fioretos [at] med [dot] lu [dot] se

Principal investigator

Translational Genomic and Functional Studies of Leucemia

+46 46 222 45 95

+46 70 334 33 67

BMC C13

66

Professor

Division of Clinical Genetics

+46 46 222 45 95

+46 70 334 33 67

BMC C13

66

Professor

Translational Genomic and Functional Studies of Leucemia

+46 46 222 45 95

+46 70 334 33 67

BMC C13

66