Discussion
The predominance of domain-specific mutations of the same gene in different cancers is mainly a manifestation of the functions driven by those domains, the upstream and downstream signaling partners, and processes that are intertwined with such domains (ref - show papers of tissue region-specific molecules interacting with respective domains. Focus on those that have greater functional relevance in those tissues).
EGFR protein has different domains that have different key roles \cite{Ferguson2008}. As a result, mutations in the gene expressing them also manifest uniquely in different cancers. For example, mutations in the tyrosine kinase domain are unique to lung cancers \cite{Purba2017}\cite{Lee2010} while brain tumors show mutations in the autoregulatory domains and the ectodomains of the same gene \cite{Wong1987}\cite{Binder2018}.
Further investigations in a larger cohort of patient samples is required to validate the role of these mutations in AA ESCC tumorigenesis. The identification of these EGFR mutations also opens the potential for targeted therapy in patients with ESCC harboring these rare mutations.