Journal
NPJ GENOMIC MEDICINE
Volume 5, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41525-020-0124-5
Keywords
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Categories
Funding
- General Research Fund (Research Grant Council, Hong Kong) [17114814]
- Research Grant Council, General Research Fund [17114814, 17121616, 14168517, R4017-18]
- Research Impact Fund
- Health and Medical Research Fund (HMRF, the Health and Medical Research Fund, the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region) [15160691]
- Hong Kong Cancer Fund, Hong Kong SAR
- School of Biomedical Sciences, Faculty of Medicine, CUHK
- National Cancer Institute, NIH, USA [1R01CA229836-01A1]
- Innovation and Technology Fund, Hong Kong government [PiH/052/18, PiH/234/18]
- Dr. Stanley Ho Medical Foundation
- General Research Fund, Research Grant Council, Hong Kong government, Hong Kong SAR [14109716, 14108818]
- HK RGC-GRF [17120718]
- University-Industry Collaboration Program (Innovation and Technology Fund, Hong Kong government, Hong Kong SAR) [UIM/329]
- University-Industry Collaboration Program (Lee's Pharmaceutical (HK) Limited) [UIM/329]
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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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