Deep sequencing of human papillomavirus positive loco-regionally advanced oropharyngeal squamous cell carcinomas reveals novel mutational signature
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- Deep sequencing of human papillomavirus positive loco-regionally advanced oropharyngeal squamous cell carcinomas reveals novel mutational signature
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BACKGROUND: The genetic profile for human papilloma virus positive (HPV+) oropharyngeal squamous cell carcinomas (OPSCC) remains largely unknown. The purpose of this study was to sequence tissue material from a large cohort of locoregionally-advanced HPV+ OPSCCs.
METHODS: We performed targeted deep sequencing of 395 cancer-associated genes in 114 matched tumor/normal loco-regionally advanced HPV+ OPSCCs. Mutations and copy number aberrations were determined.
RESULTS: We identified a total of 3459 mutations with an average of 10 mutations per megabase and a median of 28 variants per sample. The most frequently mutated genes were KALRN (28%), SPTBN1 (32%), KMT2A (31%), ZNRF3 (9%), BNC2 (12%), NOTCH2 (25%), FGFR2 (12%), SMAD2 (6%), and AR (13%). Our findings were dominated by COSMIC signature 5 and 12, represented in other head and neck cancers and in hepatocellular carcinomas, respectively.
CONCLUSIONS: We have identified multiple genetic aberrations in HPV+ OPSCCs, and the COSMIC signature 12 as most prevalent. The mutations harbour both therapeutic and prognostic potential.
Original language | English |
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Article number | 640 |
Journal | BMC Cancer |
Volume | 18 |
Issue number | 1 |
Pages (from-to) | 1-10 |
Number of pages | 10 |
ISSN | 1471-2407 |
DOIs | |
Publication status | Published - 2018 |
- Biomarkers, Tumor/genetics, DNA Mutational Analysis, High-Throughput Nucleotide Sequencing, Humans, Oropharyngeal Neoplasms/genetics, Papillomavirus Infections/complications, Squamous Cell Carcinoma of Head and Neck/genetics, Transcriptome
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