Comprehensive Genomic Analysis of Metastatic Mucinous Urethral Adenocarcinoma Guides Precision Oncology Treatment: Targetable EGFR Amplification Leading to Successful Treatment with Erlotinib

Abstract Male mucinous adenocarcinoma of the urethra (MAU) is a rare tumor for which no standards exist to guide systemic therapy. Here we describe a case of a man with MAU whose tumor was comprehensively analyzed with whole exome, long insert whole genome and transcriptome sequencing. Among many alterations, a marked amplification of EGFR was observed and immunohistochemistry (IHC) confirmed overexpression of EGFR. The patient enrolled in a clinical trial and was treated with Erlotinib, resulting in tumor shrinkage and ongoing stable disease for over one year. In addition, IHC staining for EGFR in six archival MAU tissues demonstrated that EGFR overexpression is a recurrent event in MAU. In conclusion, comprehensive genomic analysis enabled the identification of a therapeutic target in a difficult to treat tumor, MAU, and identified a potential biomarker for use in determining targeted therapies for future MAU cases.