Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5039438
- author
- organization
-
- Pathways of cancer cell evolution (research group)
- Molecular Pediatric Oncology (research group)
- Division of Clinical Genetics
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Division of Translational Cancer Research
- Division of Clinical Chemistry and Pharmacology
- Paediatrics (Lund)
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 6
- article number
- 6125
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:25625758
- wos:000348832000001
- scopus:84923088262
- pmid:25625758
- ISSN
- 2041-1723
- DOI
- 10.1038/ncomms7125
- language
- English
- LU publication?
- yes
- id
- a271e410-8ca0-408b-85f3-cba2b91fd074 (old id 5039438)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25625758?dopt=Abstract
- date added to LUP
- 2016-04-01 13:49:58
- date last changed
- 2022-03-21 20:42:36
@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.}}, 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}}, doi = {{10.1038/ncomms7125}}, volume = {{6}}, year = {{2015}}, }