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Here, we characterize the PSCC genomic landscape using whole\u2010exome sequencing. Of the 30 paired blood and tumor samples, we identified recurrent mutations in 11 genes; confirmed previous findings for <jats:italic>FAT1<\/jats:italic> (4\/30), <jats:italic>HRAS<\/jats:italic> (4\/30), <jats:italic>NOTCH1<\/jats:italic> (4\/30), <jats:italic>TP53<\/jats:italic> (3\/30) and <jats:italic>PIK3CA<\/jats:italic> (3\/30); and revealed novel candidate driver genes [<jats:italic>CASP8<\/jats:italic> (4\/30), <jats:italic>SLITRK2<\/jats:italic> (3\/30), <jats:italic>FLG<\/jats:italic> (3\/30) and <jats:italic>TRRAP<\/jats:italic> (3\/30)]. Our <jats:italic>in vitro<\/jats:italic> experiments suggested <jats:italic>CASP8<\/jats:italic> was involved in mediating TRAIL\u2010induced apoptosis of penile cancer cell lines. We also observed the frequently altered pathways for potential therapeutic implications: alterations in the Notch (30% of sample altered), RTK\u2013RAS (26.7% altered) and Hippo (23.3% altered) pathways accounted for over 50% of tumors. The frequently altered genes (&gt;10%) in these pathways were proved to be expressed in penile tumors by immunohistochemistry assay. These findings provide new insight into the mutational and pathway landscapes of PSCC and suggest potential novel therapeutic opportunities for this malignancy.<\/jats:p>","DOI":"10.1002\/ijc.32373","type":"journal-article","created":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T20:03:39Z","timestamp":1556654619000},"page":"1280-1289","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Mutational landscape of penile squamous cell carcinoma in a Chinese population"],"prefix":"10.1002","volume":"145","author":[{"given":"Yonghua","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Wang","sequence":"additional","affiliation":[{"name":"Bio\u2010X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of 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