Comparative genomic analysis of oral versus laryngeal and pharyngeal cancer

David M. Vossen, Caroline V.M. Verhagen, Marcel Verheij, Lodewyk F.A. Wessels, Conchita Vens, Michiel W.M. van den Brekel

Research output: Contribution to journalArticleScientificpeer-review

13 Citations (Scopus)

Abstract

Objective: Locally advanced oral squamous cell carcinoma (OSCC) shows lower locoregional control and disease specific survival rates than laryngeal and pharyngeal squamous cell carcinoma (L/P-SCC) after definitive chemoradiotherapy treatment. Despite clinical factors, this can point towards a different tumor biology that could impact chemoradiotherapy response rates. This prompted us to compare the mutational profiles of OSCC with L/P-SCC. Methods: We performed target capture DNA sequencing on 111 HPV-negative HNSCC samples (NKI dataset), 55 oral and 56 laryngeal/pharyngeal, and identified somatic point mutations and copy number aberrations. We next expanded our analysis with 276 OSCC and 134 L/P-SCC sample data from The Cancer Genome Atlas (TCGA dataset). We focused our analyses on genes that are frequently mutated in HNSCC. Results: The mutational profiles of OSCC and L/P-SCC showed many similarities. However, OSCC was significantly enriched for CASP8 (NKI: 15% vs 0%; TCGA: 17% vs 2%) and HRAS (TCGA: 10% vs 1%) mutations. LAMA2 (TCGA: 5% vs 19%) and NSD1 (TCGA: 7% vs 25%) mutations were enriched in L/P-SCC. Overall, we find that OSCC had fewer somatic point mutations and copy number aberrations than L/P-SCC. Interestingly, L/P-SCC scored higher in mutational and genomic scar signatures associated with homologous recombination DNA repair defects. Conclusion: Despite showing a similar mutational profile, our comparative genomic analysis revealed distinctive features in OSCC and L/P-SCC. Some of these genes and cellular processes are likely to affect the cellular response to radiation or cisplatin. Genomic characterizations may guide or enable personalized treatment in the future.

Original languageEnglish
Pages (from-to)35-44
Number of pages10
JournalOral Oncology
Volume81
DOIs
Publication statusPublished - 2018

Keywords

  • Chemoradiotherapy
  • DNA sequence analysis
  • General surgery
  • Genomics
  • Head and neck squamous cell carcinoma
  • Homologous recombination
  • Laryngeal neoplasms
  • Mutation
  • Oral cancer
  • Pharyngeal neoplasms

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