Journal
PLOS COMPUTATIONAL BIOLOGY
Volume 10, Issue 8, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pcbi.1003665
Keywords
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Funding
- NHGRI grant [U01HG006517]
- NHGRI [U54HG003079]
- International Myeloma Foundation Brian D. Novis research grant
- Barnes-Jewish Hospital Foundation grant [7603-55]
- NIH/NCI SPORE in Leukemia grant [P50CA171063]
- NIH/NCI grant [1K12CA167540]
- Clinical and Translational Award from the NIH National Center for Advancing Translational Sciences grant [UL1 TR000448]
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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.
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