Erlotinib sensitivity of MAPK1p.D321N mutation in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) lacks predictive biomarkers for drug responses. By targeted sequencing, we identified two MAPK1 mutations in recurrent HNSCC, MAPK1p.D321N, and p.R135K. We previously reported an exceptional erlotinib responder with MAPK1p.E322K. Here, by in silico and d...

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Autores principales: Ngan, Hoi-Lam, Poon, Peony Hiu Yan, Su, Yu-Xiong, Chan, Jason Ying Kuen, Lo, Kwok-Wai, Yeung, Chun Kit, Liu, Yuchen, Wong, Eileen, Li, Hui, Lau, Chin Wang, Piao, Wenying, Lui, Vivian Wai Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Brief Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171136/
https://www.ncbi.nlm.nih.gov/pubmed/32351709
http://dx.doi.org/10.1038/s41525-020-0124-5
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author Ngan, Hoi-Lam
Poon, Peony Hiu Yan
Su, Yu-Xiong
Chan, Jason Ying Kuen
Lo, Kwok-Wai
Yeung, Chun Kit
Liu, Yuchen
Wong, Eileen
Li, Hui
Lau, Chin Wang
Piao, Wenying
Lui, Vivian Wai Yan
author_facet Ngan, Hoi-Lam
Poon, Peony Hiu Yan
Su, Yu-Xiong
Chan, Jason Ying Kuen
Lo, Kwok-Wai
Yeung, Chun Kit
Liu, Yuchen
Wong, Eileen
Li, Hui
Lau, Chin Wang
Piao, Wenying
Lui, Vivian Wai Yan
author_sort Ngan, Hoi-Lam
collection PubMed
description Head and neck squamous cell carcinoma (HNSCC) lacks predictive biomarkers for drug responses. By targeted sequencing, we identified two MAPK1 mutations in recurrent HNSCC, MAPK1p.D321N, and p.R135K. We previously reported an exceptional erlotinib responder with MAPK1p.E322K. Here, by in silico and drug studies, we determined functions of these two recurrence-associated MAPK1 mutations. Residues D321, R135, and E322 are in 3D proximity. MAPK1p.D321N drives marked in vivo erlotinib sensitivity, while p.R135K’s effect is moderate.
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spelling pubmed-71711362020-04-29 Erlotinib sensitivity of MAPK1p.D321N mutation in head and neck squamous cell carcinoma Ngan, Hoi-Lam Poon, Peony Hiu Yan Su, Yu-Xiong Chan, Jason Ying Kuen Lo, Kwok-Wai Yeung, Chun Kit Liu, Yuchen Wong, Eileen Li, Hui Lau, Chin Wang Piao, Wenying Lui, Vivian Wai Yan NPJ Genom Med Brief Communication Head and neck squamous cell carcinoma (HNSCC) lacks predictive biomarkers for drug responses. By targeted sequencing, we identified two MAPK1 mutations in recurrent HNSCC, MAPK1p.D321N, and p.R135K. We previously reported an exceptional erlotinib responder with MAPK1p.E322K. Here, by in silico and drug studies, we determined functions of these two recurrence-associated MAPK1 mutations. Residues D321, R135, and E322 are in 3D proximity. MAPK1p.D321N drives marked in vivo erlotinib sensitivity, while p.R135K’s effect is moderate. Nature Publishing Group UK 2020-04-20 /pmc/articles/PMC7171136/ /pubmed/32351709 http://dx.doi.org/10.1038/s41525-020-0124-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Brief Communication
Ngan, Hoi-Lam
Poon, Peony Hiu Yan
Su, Yu-Xiong
Chan, Jason Ying Kuen
Lo, Kwok-Wai
Yeung, Chun Kit
Liu, Yuchen
Wong, Eileen
Li, Hui
Lau, Chin Wang
Piao, Wenying
Lui, Vivian Wai Yan
Erlotinib sensitivity of MAPK1p.D321N mutation in head and neck squamous cell carcinoma
title Erlotinib sensitivity of MAPK1p.D321N mutation in head and neck squamous cell carcinoma
title_full Erlotinib sensitivity of MAPK1p.D321N mutation in head and neck squamous cell carcinoma
title_fullStr Erlotinib sensitivity of MAPK1p.D321N mutation in head and neck squamous cell carcinoma
title_full_unstemmed Erlotinib sensitivity of MAPK1p.D321N mutation in head and neck squamous cell carcinoma
title_short Erlotinib sensitivity of MAPK1p.D321N mutation in head and neck squamous cell carcinoma
title_sort erlotinib sensitivity of mapk1p.d321n mutation in head and neck squamous cell carcinoma
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171136/
https://www.ncbi.nlm.nih.gov/pubmed/32351709
http://dx.doi.org/10.1038/s41525-020-0124-5
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