Targeted molecular characterization of external auditory canal squamous cell carcinomas

Hypothesis Squamous cell carcinomas (SCC) of the external auditory canal (EAC) may harbor unique genomic alterations that may explain aggressive behavior and differentiate these tumors from cutaneous SCCs of other subsites. Background EAC SCCs arise in a non-ultraviolet-exposed region of the head and neck, are often locally aggressive and may metastasize to lymph nodes or distant sites. The genomic alterations underlying cutaneous SCC of other sites are well-documented; however, mutational profiles of EAC SCC are less well characterized and may contribute to the unique anatomic site, high rates of recurrence and tumor spread. We performed targeted sequencing of a cohort of primary EAC SCCs to identify recurring and potentially targetable genomic alterations. Methods Genomic DNA was extracted from formalin-fixed paraffin-embedded specimens of 7 EAC SCCs and subjected to targeted DNA sequencing using a 227-gene panel. Somatic alterations and gene copy number alterations were annotated using our validated, in-house bioinformatics pipelines. Results In our EAC SCCs, we found recurrent alterations in TP53 and genes of receptor tyrosine kinase (eg, EGFR, FGFR) and PI3K pathways (eg, PIK3CA), similar to cutaneous SCCs of other head and neck sites. We also observed a high frequency of telomerase reverse transcriptase amplification and DNA methyltransferase 1 alterations, both of which are rarely observed in cutaneous SCCs of other sites. Conclusion These data represent the first step toward precise molecular characterization of EAC SCCs that may lead to an enhanced understanding of tumor biology and modernized precision medicine approaches for unique tumors. Level of Evidence: NA

Automated summary

Squamous cell carcinomas (SCC) of the external auditory canal (EAC) may have unique genomic alterations that explain their aggressive behavior and differentiate them from cutaneous SCCs of other sites. Recurrent alterations in TP53, EGFR, FGFR, PIK3CA, telomerase reverse transcriptase amplification, and DNA methyltransferase 1 were found in primary EAC SCCs, suggesting potential targets for precision medicine approaches.