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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.00829

Synergistic chemotherapy drug response is a genetic trait in lymphoblastoid cell lines

 Kyle Roell1, 2,  Tammy Havener3, David Reif4*, John Jack1, Howard McLeod5,  Tim Wiltshire3 and  Alison Motsinger-Reif6*
  • 1Bioinformatics Research Center, North Carolina State University, United States
  • 2Department of Statistics, College of Sciences, North Carolina State University, United States
  • 3University of North Carolina at Chapel Hill, United States
  • 4Department of Biological Sciences, College of Sciences, North Carolina State University, United States
  • 5Moffitt Cancer Center, United States
  • 6National Institute of Environmental Health Sciences (NIEHS), United States

Lymphoblastoid cell lines (LCL) are a highly successful model for evaluating the genetic etiology of cancer drug response, but applications using this model have typically focused on single drugs. Combination therapy is quite common in modern chemotherapy treatment since drugs often work synergistically, and it is an important progression in the use of the LCL model to expand work for drug combinations. In the present work, we demonstrate that synergy occurs and can be quantified in LCLs across a range of clinically important drug combinations. LCLs have been commonly employed in association mapping in cancer pharmacogenomics, but it is so far untested as to whether synergistic effects have a genetic etiology. Here we use cell lines from extended pedigrees to demonstrate that there is a substantial heritable component to synergistic drug response. Additionally, we perform linkage mapping in these pedigrees to identify putative regions linked to this important phenotype. This demonstration supports the premise of expanding the use of LCL model to perform association mapping for combination therapies.

Keywords: Synergy, heritability, chemotherapy, lymphoblastiod cell lines, linkage mapping

Received: 08 Apr 2019; Accepted: 12 Aug 2019.

Copyright: © 2019 Roell, Havener, Reif, Jack, McLeod, Wiltshire and Motsinger-Reif. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mx. David Reif, Department of Biological Sciences, College of Sciences, North Carolina State University, Raleigh, North Carolina, United States, reifdm@ncsu.edu
Dr. Alison Motsinger-Reif, National Institute of Environmental Health Sciences (NIEHS), Durham, 27709, North Carolina, United States, alison.motsinger@gmail.com