Document Type

Article

Publication Date

12-18-2018

Keywords

JMG, JGM, JAXCA

JAX Source

Sci Rep 2018 Dec 18; 8(1):17937

PMID

30560892

DOI

https://doi.org/10.1038/s41598-018-36184-8

Grant

CA034196,CA191848,CA224067,CA230031, Hope Foundation

Abstract

The processes by which tumors evolve are essential to the efficacy of treatment, but quantitative understanding of intratumoral dynamics has been limited. Although intratumoral heterogeneity is common, quantification of evolution is difficult from clinical samples because treatment replicates cannot be performed and because matched serial samples are infrequently available. To circumvent these problems we derived and assayed large sets of human triple-negative breast cancer xenografts and cell cultures from two patients, including 86 xenografts from cyclophosphamide, doxorubicin, cisplatin, docetaxel, or vehicle treatment cohorts as well as 45 related cell cultures. We assayed these samples via exome-seq and/or high-resolution droplet digital PCR, allowing us to distinguish complex therapy-induced selection and drift processes among endogenous cancer subclones with cellularity uncertainty

Comments

The authors thank Quaid Morris, Shankar Vembu, and Wei Jiao for discussions about tumor phylogenetic decomposition. The authors thank Jane Cha, Zoe Reifsnyder, and Matt Wimsatt from The Jackson Laboratory for assistance with graphics. We also thank scientific research services at The Jackson Laboratory including Doug Hinerfeld, Vanessa Spotlow, Janet Pereira, Bill Buaas, and Anuj Srivastava.

This open access article is licensed under a Creative Commons Attribution 4.0 International License

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