Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer

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. Phenotypic and genetic heterogeneity of cells within a tumour is thought to mediate treatment resistance and contribute to cancer progression. Here the authors show that genetic diversity in pediatric cancers is common after chemotherapy and can be quantified to predict survival.

• Publication year

  2015

• Venue

  Nature Communications

• Publication date

  2015-01-27

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/ncomms7125PMID 25625758
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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