Multi-modality analysis supports APOBEC as a major source of mutations in head and neck squamous cell carcinoma

Publication date: November 2017
Source:Oral Oncology, Volume 74
Author(s): Daniel L. Faden, Sean Thomas, Paul G. Cantalupo, Nishant Agrawal, Jeffrey Myers, Joseph DeRisi
ObjectivesThe 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 methodsUtilizing bioinformatic approaches we explored the role of APOBEC mediated mutations in tumor exomes, transcriptomes and germline exomes from 511HNSCC patients in the TCGA.Results58% 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.ConclusionsAPOBEC 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.



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