title: SciClone: inferring clonal architecture and tracking the spatial and temporal patterns of tumor evolution.
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.
authors.affiliation: The Genome Institute, Washington University, St. Louis, Missouri, United States of America.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Miller
authors.affiliation: 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.
authors.forename: Brian S
authors.initials: BS
authors.lastname: White
authors.affiliation: The Genome Institute, Washington University, St. Louis, Missouri, United States of America.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Dees
authors.affiliation: The Genome Institute, Washington University, St. Louis, Missouri, United States of America; Department of Genetics, Washington University, St. Louis, Missouri, United States of America.
authors.forename: Malachi
authors.initials: M
authors.lastname: Griffith
authors.affiliation: 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.
authors.forename: John S
authors.initials: JS
authors.lastname: Welch
authors.affiliation: 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.
authors.forename: Obi L
authors.initials: OL
authors.lastname: Griffith
authors.affiliation: 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.
authors.forename: Ravi
authors.initials: R
authors.lastname: Vij
authors.affiliation: 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.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Tomasson
authors.affiliation: 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.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Graubert
authors.affiliation: 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.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Walter
authors.affiliation: 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.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ellis
authors.affiliation: Liggins Institute, Auckland, New Zealand.
authors.forename: William
authors.initials: W
authors.lastname: Schierding
authors.affiliation: 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.
authors.forename: John F
authors.initials: JF
authors.lastname: DiPersio
authors.affiliation: 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.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Ley
authors.affiliation: 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.
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Mardis
authors.affiliation: 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.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Wilson
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics; D060965:Clonal Evolution / Q000235:genetics*; D019295:Computational Biology / Q000379:methods*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D015233:Models, Statistical; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000145:classification* / Q000235:genetics*; D009385:Neoplastic Processes
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