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


ABSTRACT: 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.

SUBMITTER: Ngan HL 

PROVIDER: S-EPMC7171136 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Erlotinib sensitivity of <i>MAPK1</i>p.D321N mutation in head and neck squamous cell carcinoma.

Ngan Hoi-Lam HL   Poon Peony Hiu Yan PHY   Su Yu-Xiong YX   Chan Jason Ying Kuen JYK   Lo Kwok-Wai KW   Yeung Chun Kit CK   Liu Yuchen Y   Wong Eileen E   Li Hui H   Lau Chin Wang CW   Piao Wenying W   Lui Vivian Wai Yan VWY  

NPJ genomic medicine 20200420 1


Head and neck squamous cell carcinoma (HNSCC) lacks predictive biomarkers for drug responses. By targeted sequencing, we identified two <i>MAPK1</i> mutations in recurrent HNSCC, <i>MAPK1</i>p.D321N, and p.R135K. We previously reported an exceptional erlotinib responder with <i>MAPK1</i>p.E322K. Here, by in silico and drug studies, we determined functions of these two recurrence-associated <i>MAPK1</i> mutations. Residues D321, R135, and E322 are in 3D proximity. <i>MAPK1</i>p.D321N drives marke  ...[more]

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