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Mutational landscape of penile squamous cell carcinoma in a Chinese population
Author(s) -
Wang Yonghua,
Wang Ke,
Chen Yuanbin,
Zhou Juan,
Liang Ye,
Yang Xuecheng,
Li Xiaoqi,
Cao Yanwei,
Wang Dong,
Luo Lei,
Li Bin,
Li Dan,
Wang Liping,
Liang Zhijuan,
Gao Chengwen,
Wang Qifeng,
Lv Qiang,
Li Zhiqiang,
Shi Yongyong,
Niu Haitao
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32373
Subject(s) - hras , carcinogenesis , biology , cancer research , malignancy , penile cancer , exome sequencing , exome , population , pathology , gene , cancer , mutation , genetics , medicine , kras , environmental health
Penile squamous cell carcinoma (PSCC) is a malignancy that affects the skin and tissues of the penis, but the knowledge of pathogenesis and carcinogenesis is limited. Here, we characterize the PSCC genomic landscape using whole‐exome sequencing. Of the 30 paired blood and tumor samples, we identified recurrent mutations in 11 genes; confirmed previous findings for FAT1 (4/30), HRAS (4/30), NOTCH1 (4/30), TP53 (3/30) and PIK3CA (3/30); and revealed novel candidate driver genes [ CASP8 (4/30), SLITRK2 (3/30), FLG (3/30) and TRRAP (3/30)]. Our in vitro experiments suggested CASP8 was involved in mediating TRAIL‐induced 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–RAS (26.7% altered) and Hippo (23.3% altered) pathways accounted for over 50% of tumors. The frequently altered genes (>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.