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Nat Commun. 2015 Jan 27;6:6125. doi: 10.1038/ncomms7125.

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

Author information

1
Department of Clinical Genetics, Lund University, Biomedical Center C13, SE22184 Lund, Sweden.
2
Translational Cancer Research, Department of Laboratory Medicine, Lund University, Medicon Village 404-406, SE22363 Lund, Sweden.
3
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, SE75003 Uppsala, Sweden.
4
Array and Analysis Facility, Department of Medical Sciences, Uppsala University, SE75003 Uppsala, Sweden.
5
Department of Pathology, Karolinska University Hospital, SE17176 Solna, Sweden.
6
Department of Human Genetics, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands.
7
Division of Pediatric Oncology, Department of Women's and Children's Health, Karolinska Institute, SE17165 Solna, Sweden.
8
Department of Pediatrics, Lund University, University Hospital, SE22185 Lund, Sweden.
9
Astrid Lindgren Children's Hospital, Karolinska University Hospital, SE17176 Solna, Sweden.
10
1] Department of Clinical Genetics, Lund University, Biomedical Center C13, SE22184 Lund, Sweden [2] Department of Pathology, Skåne Regional and University Laboratories, SE22185 Lund, Sweden.

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.

PMID:
25625758
DOI:
10.1038/ncomms7125
[Indexed for MEDLINE]

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