Gene mutations in primary tumors and corresponding patient-derived xenografts derived from non-small cell lung cancer

Chuncheng Hao, Li Wang, Shaohua Peng, Mengru Cao, Hongyu Li, Jing Hu, Xiao Huang, Wei Liu, Hui Zhang, Shuhong Wu, Apar Pataer, John V. Heymach, Agda Karina Eterovic, Qingxiu Zhang, Kenna R. Shaw, Ken Chen, Andrew Futreal, Michael Wang, Wayne Hofstetter, Reza MehranDavid Rice, Jack A. Roth, Boris Sepesi, Stephen G. Swisher, Ara Vaporciyan, Garrett L. Walsh, Faye M. Johnson, Bingliang Fang

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Molecular annotated patient-derived xenograft (PDX) models are useful for the preclinical investigation of anticancer drugs and individualized anticancer therapy. We established 23 PDXs from 88 surgical specimens of lung cancer patients and determined gene mutations in these PDXs and their paired primary tumors by ultradeep exome sequencing on 202 cancer-related genes. The numbers of primary tumors with deleterious mutations in TP53, KRAS, PI3KCA, ALK, STK11, and EGFR were 43.5%, 21.7%, 17.4%, 17.4%, 13.0%, and 8.7%, respectively. Other genes with deleterious mutations in ≥3 (13.0%) primary tumors were MLL3, SETD2, ATM, ARID1A, CRIPAK, HGF, BAI3, EP300, KDR, PDGRRA and RUNX1. Of 315 mutations detected in the primary tumors, 293 (93%) were also detected in their corresponding PDXs, indicating that PDXs have the capacity to recapitulate the mutations in primary tumors. Nevertheless, a substantial number of mutations had higher allele frequencies in the PDXs than in the primary tumors, or were not detectable in the primary tumor, suggesting the possibility of tumor cell enrichment in PDXs or heterogeneity in the primary tumors. The molecularly annotated PDXs generated from this study could be useful for future translational studies.

Original languageEnglish (US)
Pages (from-to)179-185
Number of pages7
JournalCancer Letters
Volume357
Issue number1
DOIs
StatePublished - Feb 1 2015

Keywords

  • Biomarkers
  • Gene mutations
  • Lung cancer
  • Patient-derived xenografts
  • Tumor models

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hao, C., Wang, L., Peng, S., Cao, M., Li, H., Hu, J., Huang, X., Liu, W., Zhang, H., Wu, S., Pataer, A., Heymach, J. V., Eterovic, A. K., Zhang, Q., Shaw, K. R., Chen, K., Futreal, A., Wang, M., Hofstetter, W., ... Fang, B. (2015). Gene mutations in primary tumors and corresponding patient-derived xenografts derived from non-small cell lung cancer. Cancer Letters, 357(1), 179-185. https://doi.org/10.1016/j.canlet.2014.11.024