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

Oral Oncology
Daniel L FadenJoseph DeRisi

Abstract

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. Utilizing bioinformatic approaches we explored the role of APOBEC mediated mutations in tumor exomes, transcriptomes and germline exomes from 511HNSCC patients in the TCGA. 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. 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 th...Continue Reading

Citations

Nov 22, 2018·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M OlivaL L Siu
Mar 21, 2019·Current Opinion in Oncology·Esma Saada-BouzidJoël Guigay
Sep 2, 2020·The Journal of Experimental Medicine·Emily K LawReuben S Harris
Sep 16, 2020·International Journal of Cancer. Journal International Du Cancer·Michaela PlathKarim Zaoui
Aug 1, 2018·Scientific Reports·Tingting QinMaureen A Sartor
Mar 1, 2019·Frontiers in Oncology·Esma Saada-Bouzid, Christophe Le Tourneau
Jul 8, 2020·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Prokopios P ArgyrisReuben S Harris
Feb 13, 2021·International Journal of Molecular Sciences·Giuseppe RivaValentina Dell'Oste
Mar 4, 2021·NAR Genomics and Bioinformatics·Maoxuan LinJun-Tao Guo

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