Oral Squamous Cell Carcinoma in Young Patients Show Higher Rates of EGFR Amplification: Implications for Novel Personalized Therapy

There is an increasing worldwide incidence of patients under 50 years of age presenting with oral squamous cell carcinoma (OSCC). The molecular mechanisms driving disease in this emerging cohort remain unclear, limiting impactful treatment options for these patients. To identify common clinically ac...

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Autores principales:	Laveniya Satgunaseelan, Sean Porazinski, Dario Strbenac, Aji Istadi, Cali Willet, Tracy Chew, Rosemarie Sadsad, Carsten E. Palme, Jenny H. Lee, Michael Boyer, Jean Y. H. Yang, Jonathan R. Clark, Marina Pajic, Ruta Gupta
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	oral squamous cell carcinoma EGFR genomics personalized therapy tumor mutation burden Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/693a649c31a8476a9a20a57ba960f116
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spelling	oai:doaj.org-article:693a649c31a8476a9a20a57ba960f1162021-12-01T13:16:23ZOral Squamous Cell Carcinoma in Young Patients Show Higher Rates of EGFR Amplification: Implications for Novel Personalized Therapy2234-943X10.3389/fonc.2021.750852https://doaj.org/article/693a649c31a8476a9a20a57ba960f1162021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.750852/fullhttps://doaj.org/toc/2234-943XThere is an increasing worldwide incidence of patients under 50 years of age presenting with oral squamous cell carcinoma (OSCC). The molecular mechanisms driving disease in this emerging cohort remain unclear, limiting impactful treatment options for these patients. To identify common clinically actionable targets in this cohort, we used whole genome and transcriptomic sequencing of OSCC patient samples from 26 individuals under 50 years of age. These molecular profiles were compared with those of OSCC patients over 50 years of age (n=11) available from TCGA. We show for the first time that a molecular signature comprising of EGFR amplification and increased EGFR RNA abundance is specific to the young subset of OSCC patients. Furthermore, through functional assays using patient tumor-derived cell lines, we reveal that this EGFR amplification results in increased activity of the EGFR pathway. Using a panel of clinically relevant EGFR inhibitors we determine that an EGFR-amplified patient-derived cell line is responsive to EGFR inhibition, suggesting EGFR amplification represents a valid therapeutic target in this subset of OSCC patients. In particular, we demonstrate sensitivity to the second-generation EGFR tyrosine kinase inhibitor afatinib, which offers a new and promising therapeutic avenue versus current EGFR-targeting approaches. We propose that testing for EGFR amplification could easily be integrated into current diagnostic workflows and such measures could lead to more personalized treatment approaches and improved outcomes for this younger cohort of OSCC patients.Laveniya SatgunaseelanLaveniya SatgunaseelanSean PorazinskiSean PorazinskiDario StrbenacAji IstadiCali WilletTracy ChewRosemarie SadsadCarsten E. PalmeJenny H. LeeMichael BoyerMichael BoyerJean Y. H. YangJean Y. H. YangJonathan R. ClarkJonathan R. ClarkJonathan R. ClarkMarina PajicMarina PajicRuta GuptaRuta GuptaRuta GuptaFrontiers Media S.A.articleoral squamous cell carcinomaEGFRgenomicspersonalized therapytumor mutation burdenNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	oral squamous cell carcinoma EGFR genomics personalized therapy tumor mutation burden Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	oral squamous cell carcinoma EGFR genomics personalized therapy tumor mutation burden Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Laveniya Satgunaseelan Laveniya Satgunaseelan Sean Porazinski Sean Porazinski Dario Strbenac Aji Istadi Cali Willet Tracy Chew Rosemarie Sadsad Carsten E. Palme Jenny H. Lee Michael Boyer Michael Boyer Jean Y. H. Yang Jean Y. H. Yang Jonathan R. Clark Jonathan R. Clark Jonathan R. Clark Marina Pajic Marina Pajic Ruta Gupta Ruta Gupta Ruta Gupta Oral Squamous Cell Carcinoma in Young Patients Show Higher Rates of EGFR Amplification: Implications for Novel Personalized Therapy
description	There is an increasing worldwide incidence of patients under 50 years of age presenting with oral squamous cell carcinoma (OSCC). The molecular mechanisms driving disease in this emerging cohort remain unclear, limiting impactful treatment options for these patients. To identify common clinically actionable targets in this cohort, we used whole genome and transcriptomic sequencing of OSCC patient samples from 26 individuals under 50 years of age. These molecular profiles were compared with those of OSCC patients over 50 years of age (n=11) available from TCGA. We show for the first time that a molecular signature comprising of EGFR amplification and increased EGFR RNA abundance is specific to the young subset of OSCC patients. Furthermore, through functional assays using patient tumor-derived cell lines, we reveal that this EGFR amplification results in increased activity of the EGFR pathway. Using a panel of clinically relevant EGFR inhibitors we determine that an EGFR-amplified patient-derived cell line is responsive to EGFR inhibition, suggesting EGFR amplification represents a valid therapeutic target in this subset of OSCC patients. In particular, we demonstrate sensitivity to the second-generation EGFR tyrosine kinase inhibitor afatinib, which offers a new and promising therapeutic avenue versus current EGFR-targeting approaches. We propose that testing for EGFR amplification could easily be integrated into current diagnostic workflows and such measures could lead to more personalized treatment approaches and improved outcomes for this younger cohort of OSCC patients.
format	article
author	Laveniya Satgunaseelan Laveniya Satgunaseelan Sean Porazinski Sean Porazinski Dario Strbenac Aji Istadi Cali Willet Tracy Chew Rosemarie Sadsad Carsten E. Palme Jenny H. Lee Michael Boyer Michael Boyer Jean Y. H. Yang Jean Y. H. Yang Jonathan R. Clark Jonathan R. Clark Jonathan R. Clark Marina Pajic Marina Pajic Ruta Gupta Ruta Gupta Ruta Gupta
author_facet	Laveniya Satgunaseelan Laveniya Satgunaseelan Sean Porazinski Sean Porazinski Dario Strbenac Aji Istadi Cali Willet Tracy Chew Rosemarie Sadsad Carsten E. Palme Jenny H. Lee Michael Boyer Michael Boyer Jean Y. H. Yang Jean Y. H. Yang Jonathan R. Clark Jonathan R. Clark Jonathan R. Clark Marina Pajic Marina Pajic Ruta Gupta Ruta Gupta Ruta Gupta
author_sort	Laveniya Satgunaseelan
title	Oral Squamous Cell Carcinoma in Young Patients Show Higher Rates of EGFR Amplification: Implications for Novel Personalized Therapy
title_short	Oral Squamous Cell Carcinoma in Young Patients Show Higher Rates of EGFR Amplification: Implications for Novel Personalized Therapy
title_full	Oral Squamous Cell Carcinoma in Young Patients Show Higher Rates of EGFR Amplification: Implications for Novel Personalized Therapy
title_fullStr	Oral Squamous Cell Carcinoma in Young Patients Show Higher Rates of EGFR Amplification: Implications for Novel Personalized Therapy
title_full_unstemmed	Oral Squamous Cell Carcinoma in Young Patients Show Higher Rates of EGFR Amplification: Implications for Novel Personalized Therapy
title_sort	oral squamous cell carcinoma in young patients show higher rates of egfr amplification: implications for novel personalized therapy
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/693a649c31a8476a9a20a57ba960f116
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Oral Squamous Cell Carcinoma in Young Patients Show Higher Rates of EGFR Amplification: Implications for Novel Personalized Therapy

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