Multi-modality analysis supports APOBEC as a major source of mutations in head and neck squamous cell carcinoma. (November 2017)

• Record Type: Journal Article
• Authors: Faden, Daniel L.; Thomas, Sean; Cantalupo, Paul G.; Agrawal, Nishant; Myers, Jeffrey; DeRisi, Joseph
• Is Part Of: Oral oncology. Volume 74(2017)
• Page Start: 8
• Page End: 14
• Publication Date: 2017-11
• Subjects: APOBEC -- Head and neck squamous cell carcinoma -- Human papilloma virus -- Mutational signature; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2017.09.002
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: APOBEC mutations are highly prevalent in HNSCC. APOBEC gene-specific analysis and expression analysis support APOBEC3A as the most likely APOBEC gene active in HNSCC. Immune pathway upregulation is coincident with APOBEC activity in HNSCC. Abstract: Objectives: The mutagenic processes underlying head and neck squamous cell carcinoma (HNSCC) are poorly understood. Pan-cancer mutational signature analyses have identified a signature for APOBEC, a cytosine deaminase, in a subset of cancers, including HNSCC. The role of APOBEC activity in HNSCC remains poorly understood. Therefore, we sought to determine the role of APOBEC in HNSCC pathogenesis. Material and methods: Utilizing bioinformatic approaches we explored the role of APOBEC mediated mutations in tumor exomes, transcriptomes and germline exomes from 511 HNSCC patients in the TCGA. Results: 58% of HNSCC were statistically enriched for the APOBEC signature. APOBEC3A expression had the highest correlation coefficient with APOBEC mutation rate. Gene specific motif analysis revealed a slight predominance of APOBEC3A mutations. Canonical pathway analysis demonstrated immune pathway upregulation in APOBEC mutation rich samples. Overall mutational burden was positively correlated with APOBEC enrichment. Conclusions: APOBEC mediated mutations are highly prevalent in HNSCC. APOBEC3A is the most likely gene to be active in HPV+ HNSCC. APOBEC activity correlates with upregulation of immune signaling pathways, supporting the hypothesis that APOBEC activity could be activated as part of the innate immune response.