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PLoS Comput Biol. 2014 Aug 7;10(8):e1003665. doi: 10.1371/journal.pcbi.1003665. eCollection 2014 Aug.

SciClone: inferring clonal architecture and tracking the spatial and temporal patterns of tumor evolution.

Author information

1
The Genome Institute, Washington University, St. Louis, Missouri, United States of America.
2
The Genome Institute, Washington University, St. Louis, Missouri, United States of America; Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
3
The Genome Institute, Washington University, St. Louis, Missouri, United States of America; Department of Genetics, Washington University, St. Louis, Missouri, United States of America.
4
Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, United States of America; Siteman Cancer Center, Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri, United States of America.
5
Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, United States of America; Siteman Cancer Center, Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri, United States of America; Massachusetts General Hospital, Boston, Massachusetts, United States of America.
6
Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, United States of America; Department of Genetics, Washington University, St. Louis, Missouri, United States of America; Siteman Cancer Center, Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri, United States of America.
7
Liggins Institute, Auckland, New Zealand.
8
The Genome Institute, Washington University, St. Louis, Missouri, United States of America; Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, United States of America; Department of Genetics, Washington University, St. Louis, Missouri, United States of America; Siteman Cancer Center, Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, Missouri, United States of America.

Abstract

The sensitivity of massively-parallel sequencing has confirmed that most cancers are oligoclonal, with subpopulations of neoplastic cells harboring distinct mutations. A fine resolution view of this clonal architecture provides insight into tumor heterogeneity, evolution, and treatment response, all of which may have clinical implications. Single tumor analysis already contributes to understanding these phenomena. However, cryptic subclones are frequently revealed by additional patient samples (e.g., collected at relapse or following treatment), indicating that accurately characterizing a tumor requires analyzing multiple samples from the same patient. To address this need, we present SciClone, a computational method that identifies the number and genetic composition of subclones by analyzing the variant allele frequencies of somatic mutations. We use it to detect subclones in acute myeloid leukemia and breast cancer samples that, though present at disease onset, are not evident from a single primary tumor sample. By doing so, we can track tumor evolution and identify the spatial origins of cells resisting therapy.

PMID:
25102416
PMCID:
PMC4125065
DOI:
10.1371/journal.pcbi.1003665
[Indexed for MEDLINE]
Free PMC Article
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