Comparative genomic analysis of oral versus laryngeal and pharyngeal cancer

• Main Authors: van den Brekel, M.W.M (Author), Vens, C. (Author), Verhagen, C.V.M (Author), Verheij, M. (Author), Vossen, D.M (Author), Wessels, L.F.A (Author)
• Format: Article
• Language: English
• Published: Elsevier Ltd 2018
• Subjects: adult; aged; Aged; allelic imbalance; Article; bioinformatics; Carcinoma, Squamous Cell; casp8 protein; CASP8 protein, human; caspase 8; Caspase 8; Chemoradiotherapy; clinical outcome; comparative genomic hybridization; Comparative Genomic Hybridization; comparative study; copy number variation; DNA sequence; DNA sequence analysis; female; Female; gene frequency; General surgery; Genes, ras; genetic analysis; genetics; genomics; Genomics; Head and neck squamous cell carcinoma; homologous recombination; Homologous recombination; hras protein; human; human tissue; Humans; laminin alpha2; Laryngeal neoplasms; Laryngeal Neoplasms; larynx squamous cell carcinoma; larynx tumor; major clinical study; male; Male; middle aged; Middle Aged; Mouth Neoplasms; mouth squamous cell carcinoma; mouth tumor; Mutation; nonhuman; nsd1 protein; oncogene ras; Oral cancer; oropharynx squamous cell carcinoma; Pharyngeal neoplasms; Pharyngeal Neoplasms; pharynx cancer; point mutation; Point Mutation; priority journal; protein; recombination repair; Retrospective Studies; retrospective study; somatic mutation; squamous cell carcinoma; unclassified drug; Wart virus
• Online Access: View Fulltext in Publisher

 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. © 2018