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

Hoi Lam Ngan, Peony Hiu Yan Poon, Yu Xiong Su, Jason Ying Kuen Chan, Kwok Wai Lo, Chun Kit Yeung, Yuchen Liu, Eileen Wong, Hui Li, Chin Wang Lau, Wenying Piao, Vivian Wai Yan Lui

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Article number17
Journalnpj Genomic Medicine
Volume5
Issue number1
DOIs
StatePublished - Dec 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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