Characterization of squamous cell lung cancers from Appalachian Kentucky

Jinpeng Liu, Thilakam Murali, Tianxin Yu, Chunming Liu, Theru A. Sivakumaran, Hunter N.B. Moseley, Igor B. Zhulin, Heidi L. Weiss, Eric B. Durbin, Sally R. Ellingson, Jinze Liu, Bin Huang, Brent J. Hallahan, Craig M. Horbinski, Kurt Hodges, Dana L. Napier, Thèrése Bocklage, Joseph Mueller, Nathan L. Vanderford, David W. FardoChi Wang, Susanne M. Arnold

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Background: Lung cancer is the leading cause of cancer mortality in the United States (U.S.). Squamous cell carcinoma (SQCC) represents 22.6% of all lung cancers nationally, and 26.4% in Appalachian Kentucky (AppKY), where death from lung cancer is exceptionally high. The Cancer Genome Atlas (TCGA) characterized genetic alterations in lung SQCC, but this cohort did not focus on AppKY residents. Methods: Whole-exome sequencing was performed on tumor and normal DNA samples from 51 lung SQCC subjects from AppKY. Somatic genomic alterations were compared between the AppKY and TCGA SQCC cohorts. Results: From this AppKY cohort, we identified an average of 237 nonsilent mutations per patient and, in comparison with TCGA, we found that PCMTD1 (18%) and IDH1 (12%) were more commonly altered in AppKY versus TCGA. Using IDH1 as a starting point, we identified a mutually exclusive mutational pattern (IDH1, KDM6A, KDM4E, JMJD1C) involving functionally related genes. We also found actionable mutations (10%) and/or intermediate or high-tumor mutation burden (65%), indicating potential therapeutic targets in 65% of subjects. Conclusions: This study has identified an increased percentage of IDH1 and PCMTD1 mutations in SQCC arising in the AppKY residents versus TCGA, with population-specific implications for the personalized treatment of this disease. Impact: Our study is the first report to characterize genomic alterations in lung SQCC from AppKY. These findings suggest population differences in the genetics of lung SQCC between AppKY and U.S. populations, highlighting the importance of the relevant population when developing personalized treatment approaches for this disease.

Original languageEnglish
Pages (from-to)348-356
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Issue number2
StatePublished - Feb 2019

Bibliographical note

Funding Information:
The authors wish to thank Drs. Jill M. Kolesar and Andrew N. Lane for helpful comments, the MCC Research Communications Office for its assistance in manuscript editing and Dr. Youngwook Kim for providing the somatic mutation and copy number variation data from their paper (30). T. Murali, H.N.B. Moseley and C. Wang were supported by NCI (grant no. R21 CA205778). I.B. Zhulin was supported by National Institute of General Medical Sciences (grant no. R01 GM072285). H.L. Weiss, J. Liu, C. Wang and S.M. Arnold were supported by NIH (grant no. UL1 TR001998). This work was also supported by NCI grant P30 CA177558 which supports the Biostatistics and Bioinformatics SRF, the Biospecimen Procurement and Translation Pathology SRF, and the Cancer Research Informatics SRF of the University of Kentucky MCC.

Publisher Copyright:
© 2018 American Association for Cancer Research.

ASJC Scopus subject areas

  • Epidemiology
  • Oncology


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