Journal Article

SciClone: Inferring Clonal Architecture and Tracking the Spatial and Temporal Patterns of Tumor Evolution

Griffith, Obi L., Vij, Ravi, Graubert, Timothy A., Mardis, Elaine R., Miller, Christopher A., Wilson, Richard K., White, Brian S., Griffith, Malachi, Welch, John S., Walter, Matthew J., Tomasson, Michael H., Ellis, Matthew J., Schierding, William, DiPersio, John F., Dees, Nathan D., Ley, Timothy J., Ding, Li

2014

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Architecture / Biology and Life Sciences / Breast cancer / Breast Neoplasms - genetics / Cancer / Cancer therapies / Clonal Evolution - genetics / Cloning / Computational Biology - methods / Female / Gene Frequency - genetics / Genetic aspects / Genetic research / Health aspects / Humans / Leukemia / Leukemia, Myeloid, Acute - genetics / Medicine and Health Sciences / Metastasis / Methods / Models, Statistical / Multiple myeloma / Mutation - genetics / Neoplasms - classification / Neoplasms - genetics / Neoplastic Processes / Oncology, Experimental / Studies / Tumors