Gene mutations in primary tumors and corresponding patient-derived xenografts derived from non-small cell lung cancer. Issue 1 (1st February 2015)

• Record Type: Journal Article
• Authors: Hao, Chuncheng; Wang, Li; Peng, Shaohua; Cao, Mengru; Li, Hongyu; Hu, Jing; Huang, Xiao; Liu, Wei; Zhang, Hui; Wu, Shuhong; Pataer, Apar; Heymach, John V.; Eterovic, Agda Karina; Zhang, Qingxiu; Shaw, Kenna R.; Chen, Ken; Futreal, Andrew; Wang, Michael; Hofstetter, Wayne; Mehran, Reza; Rice, David; Roth, Jack A.; Sepesi, Boris; Swisher, Stephen G.; Vaporciyan, Ara; Walsh, Garrett L.; Johnson, Faye M.; Fang, Bingliang
• Is Part Of: Cancer letters. Volume 357:Issue 1(2015)
• Page Start: 179
• Page End: 185
• Publication Date: 2015-02-01
• Subjects: Lung cancer -- Gene mutations -- Tumor models -- Patient-derived xenografts -- Biomarkers; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2014.11.024
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: 23 PDXs from lung cancer and their primary tumors were sequenced by exome sequencing analysis on 202 cancer-related genes. Numbers of primary tumors with mutations in TP53, KRAS, PI3KCA, ALK, STK11, and EGFR were 10, 5, 4, 4, 3, and 2, respectively. Other genes with mutations in ≥3 tumors were MLL3, SETD2, ATM, ARID1A, CRIPAK, HGF, BAI3, EP300, KDR, PDGRRA and RUNX1 . 93% of mutations detected in the primary tumors were also detected in their corresponding PDXs. Some mutations had higher allele frequencies in the PDXs than in the primary tumors, suggesting tumor cell enrichment in PDXs. 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.