title: Identification of somatic gene mutations in penile squamous cell carcinoma.
abstract: There is a lack of studies on somatic gene mutations and cell signaling driving penile carcinogenesis. Our objective was to analyze somatic mutations in genes downstream of EGFR in penile squamous cell carcinomas, especially the mTOR and RAS/MAPK pathways. We retrospectively analyzed somatic mutations in 10 in situ and 65 invasive penile squamous cell carcinomas by using Sequenom's Mass Spectrometry iPlex Technology and Oncocarta v1.0 Panel. The DNA was extracted from FFPE blocks and we identified somatic missense mutations in three in situ tumors and in 19 invasive tumors, mostly in PIK3CA, KRAS, HRAS, NRAS, and PDGFA genes. Somatic mutations in the PIK3CA gene or RAS family genes were neither associated with tumor grade, stage or outcome, and were equally often identified in hrHPV positive and in hrHPV negative tumors that showed no p53 expression. Mutations in PIK3CA, KRAS, and HRAS are frequent in penile squamous cell carcinoma and likely play a role in the development of p53-negative tumors. Although the presence of these mutations does not seem to correlate with tumoral behavior or outcome, they could be biomarkers of treatment failure with anti-EGFR mAb in patients with penile squamous cell carcinoma.
authors.affiliation: Dermatology Department, Hospital Universitari Vall D'hebron, Barcelona, Spain.|Faculty of Medicine, Universitat Autònoma De Barcelona, Barcelona, Spain.
authors.forename: Carla
authors.initials: C
authors.lastname: Ferrándiz-Pulido
authors.affiliation: Faculty of Medicine, Universitat Autònoma De Barcelona, Barcelona, Spain.|Pathology Department, Hospital Universitari Vall D'hebron, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Hernández-Losa
authors.affiliation: Dermatology Department, Hospital Del Mar-IMIM, Barcelona, Spain.|Faculty of Medicine, Universitat De Barcelona, Barcelona, Spain.
authors.forename: Emili
authors.initials: E
authors.lastname: Masferrer
authors.affiliation: Vall D'Hebron Institute of Oncology, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Vivancos
authors.affiliation: Pathology Department, Hospital Universitari Vall D'hebron, Barcelona, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Somoza
authors.affiliation: Pathology Department, Hospital Universitari Vall D'hebron, Barcelona, Spain.
authors.forename: Roso
authors.initials: R
authors.lastname: Marés
authors.affiliation: Faculty of Medicine, Universitat Autònoma De Barcelona, Barcelona, Spain.|Oncology Department, Hospital Universitari Vall D'hebron, Barcelona, Spain.
authors.forename: Claudia
authors.initials: C
authors.lastname: Valverde
authors.affiliation: Faculty of Medicine, Universitat Autònoma De Barcelona, Barcelona, Spain.|Urology Department, Hospital Universitari Vall D'hebron, Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Salvador
authors.affiliation: Faculty of Medicine, Universitat Autònoma De Barcelona, Barcelona, Spain.|Urology Department, Hospital Universitari Vall D'hebron, Barcelona, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Placer
authors.affiliation: Faculty of Medicine, Universitat Autònoma De Barcelona, Barcelona, Spain.|Urology Department, Hospital Universitari Vall D'hebron, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Morote
authors.affiliation: Dermatology Department, Hospital Del Mar-IMIM, Barcelona, Spain.|Faculty of Medicine, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Pujol
authors.forename: Santiago
authors.initials: S
authors.lastname: Ramon y Cajal
authors.affiliation: Faculty of Medicine, Universitat Autònoma De Barcelona, Barcelona, Spain.|Pathology Department, Hospital Universitari Vall D'hebron, Barcelona, Spain.
authors.forename: Ines
authors.initials: I
authors.lastname: de Torres
authors.affiliation: Dermatology Department, Hospital Del Mar-IMIM, Barcelona, Spain.|Faculty of Medicine, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Agusti
authors.initials: A
authors.lastname: Toll
authors.affiliation: Dermatology Department, Hospital Universitari Vall D'hebron, Barcelona, Spain.|Faculty of Medicine, Universitat Autònoma De Barcelona, Barcelona, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: García-Patos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010412:Penile Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C546842:MTOR protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D058570:TOR Serine-Threonine Kinases