Novel insight into mutational landscape of head and neck squamous cell carcinoma

Daria A. Gaykalova, Elizabeth Mambo, Ashish Choudhary, Jeffery Houghton, Kalyan Buddavarapu, Tiffany Sanford, Will Darden, Alex Adai, Andrew Hadd, Gary Latham, Ludmila V. Danilova, Justin Bishop, Ryan Li, William H. Westra, Patrick Hennessey, Wayne M. Koch, Michael F. Ochs, Joseph A. Califano, Wenyue Sun

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Development of head and neck squamous cell carcinoma (HNSCC) is characterized by accumulation of mutations in several oncogenes and tumor suppressor genes. We have formerly described the mutation pattern of HNSCC and described NOTCH signaling pathway alterations. Given the complexity of the HNSCC, here we extend the previous study to understand the overall HNSCC mutation context and to discover additional genetic alterations. We performed high depth targeted exon sequencing of 51 highly actionable cancer-related genes with a high frequency of mutation across many cancer types, including head and neck. DNA from primary tumor tissues and matched normal tissues was analyzed for 37 HNSCC patients. We identified 26 non-synonymous or stop-gained mutations targeting 11 of 51 selected genes. These genes were mutated in 17 out of 37 (46%) studied HNSCC patients. Smokers harbored 3.2-fold more mutations than non-smokers. Importantly, TP53 was mutated in 30%, NOTCH1 in 8% and FGFR3 in 5% of HNSCC. HPV negative patients harbored 4-fold more TP53 mutations than HPV positive patients. These data confirm prior reports of the HNSCC mutational profile. Additionally, we detected mutations in two new genes, CEBPA and FES, which have not been previously reported in HNSCC. These data extend the spectrum of HNSCC mutations and define novel mutation targets in HNSCC carcinogenesis, especially for smokers and HNSCC without HPV infection.

Original languageEnglish (US)
Article numbere93102
JournalPLoS One
Volume9
Issue number3
DOIs
StatePublished - Mar 25 2014
Externally publishedYes

Fingerprint

squamous cell carcinoma
neck
mutation
Mutation
Genes
Carcinoma, squamous cell of head and neck
Epithelial Cells
Tumors
neoplasms
genes
Tissue
Neoplasm Genes
tumor suppressor genes
Mutation Rate
oncogenes
Head and Neck Neoplasms
Tumor Suppressor Genes
Oncogenes
carcinogenesis
Exons

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Gaykalova, D. A., Mambo, E., Choudhary, A., Houghton, J., Buddavarapu, K., Sanford, T., ... Sun, W. (2014). Novel insight into mutational landscape of head and neck squamous cell carcinoma. PLoS One, 9(3), [e93102]. https://doi.org/10.1371/journal.pone.0093102

Novel insight into mutational landscape of head and neck squamous cell carcinoma. / Gaykalova, Daria A.; Mambo, Elizabeth; Choudhary, Ashish; Houghton, Jeffery; Buddavarapu, Kalyan; Sanford, Tiffany; Darden, Will; Adai, Alex; Hadd, Andrew; Latham, Gary; Danilova, Ludmila V.; Bishop, Justin; Li, Ryan; Westra, William H.; Hennessey, Patrick; Koch, Wayne M.; Ochs, Michael F.; Califano, Joseph A.; Sun, Wenyue.

In: PLoS One, Vol. 9, No. 3, e93102, 25.03.2014.

Research output: Contribution to journalArticle

Gaykalova, DA, Mambo, E, Choudhary, A, Houghton, J, Buddavarapu, K, Sanford, T, Darden, W, Adai, A, Hadd, A, Latham, G, Danilova, LV, Bishop, J, Li, R, Westra, WH, Hennessey, P, Koch, WM, Ochs, MF, Califano, JA & Sun, W 2014, 'Novel insight into mutational landscape of head and neck squamous cell carcinoma', PLoS One, vol. 9, no. 3, e93102. https://doi.org/10.1371/journal.pone.0093102
Gaykalova DA, Mambo E, Choudhary A, Houghton J, Buddavarapu K, Sanford T et al. Novel insight into mutational landscape of head and neck squamous cell carcinoma. PLoS One. 2014 Mar 25;9(3). e93102. https://doi.org/10.1371/journal.pone.0093102
Gaykalova, Daria A. ; Mambo, Elizabeth ; Choudhary, Ashish ; Houghton, Jeffery ; Buddavarapu, Kalyan ; Sanford, Tiffany ; Darden, Will ; Adai, Alex ; Hadd, Andrew ; Latham, Gary ; Danilova, Ludmila V. ; Bishop, Justin ; Li, Ryan ; Westra, William H. ; Hennessey, Patrick ; Koch, Wayne M. ; Ochs, Michael F. ; Califano, Joseph A. ; Sun, Wenyue. / Novel insight into mutational landscape of head and neck squamous cell carcinoma. In: PLoS One. 2014 ; Vol. 9, No. 3.
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