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Novel Insight into Mutational Landscape of Head and Neck Squamous Cell Carcinoma

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, h...

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Autores principales: 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 J., Westra, William H., Hennessey, Patrick, Koch, Wayne M., Ochs, Michael F., Califano, Joseph A., Sun, Wenyue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3965530/
https://www.ncbi.nlm.nih.gov/pubmed/24667986
http://dx.doi.org/10.1371/journal.pone.0093102
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author 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 J.
Westra, William H.
Hennessey, Patrick
Koch, Wayne M.
Ochs, Michael F.
Califano, Joseph A.
Sun, Wenyue
author_facet 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 J.
Westra, William H.
Hennessey, Patrick
Koch, Wayne M.
Ochs, Michael F.
Califano, Joseph A.
Sun, Wenyue
author_sort Gaykalova, Daria A.
collection PubMed
description 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.
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spelling pubmed-39655302014-03-27 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 J. Westra, William H. Hennessey, Patrick Koch, Wayne M. Ochs, Michael F. Califano, Joseph A. Sun, Wenyue PLoS One Research Article 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. Public Library of Science 2014-03-25 /pmc/articles/PMC3965530/ /pubmed/24667986 http://dx.doi.org/10.1371/journal.pone.0093102 Text en © 2014 Gaykalova et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
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 J.
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
title Novel Insight into Mutational Landscape of Head and Neck Squamous Cell Carcinoma
title_full Novel Insight into Mutational Landscape of Head and Neck Squamous Cell Carcinoma
title_fullStr Novel Insight into Mutational Landscape of Head and Neck Squamous Cell Carcinoma
title_full_unstemmed Novel Insight into Mutational Landscape of Head and Neck Squamous Cell Carcinoma
title_short Novel Insight into Mutational Landscape of Head and Neck Squamous Cell Carcinoma
title_sort novel insight into mutational landscape of head and neck squamous cell carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3965530/
https://www.ncbi.nlm.nih.gov/pubmed/24667986
http://dx.doi.org/10.1371/journal.pone.0093102
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