Penile squamous cell carcinoma (PSCC) is a rare but aggressive neoplasm with dual pathogenesis (human papillomavirus (HPV)-associated and HPV-independent). The development of targeted treatment is hindered by poor knowledge of the molecular landscape of PSCC. We performed a thorough review of genetic alterations of PSCC focused on somatic mutations and/or copy number alterations. A total of seven articles have been identified which, overall, include 268 PSCC. However, the series are heterogeneous regarding methodologies employed for DNA sequencing and HPV detection together with HPV prevalence, and include, in general, a limited number of cases, which results in markedly different findings. Reported top-ranked mutations involve TP53, CDKN2A, FAT1, NOTCH-1 and PIK3CA. Numerical alterations involve gains in MYC and EGFR, as well as amplifications in HPV integration loci. A few genes including TP53, CDKN2A, PIK3CA and CCND1 harbor both somatic mutations and copy number alterations. Notch, RTK-RAS and Hippo pathways are frequently deregulated. Nevertheless, the relevance of the identified alterations, their role in signaling pathways or their association with HPV status remain elusive. Combined targeting of different pathways might represent a valid therapeutic approach in PSCC. This work calls for large-scale sequencing studies with robust HPV testing to improve the genomic understanding of PSCC.
International journal of molecular sciences. 2021 Dec 27*** epublish ***
Inmaculada Ribera-Cortada, José Guerrero-Pineda, Isabel Trias, Luis Veloza, Adriana Garcia, Lorena Marimon, Sherley Diaz-Mercedes, José Ramon Alamo, Maria Teresa Rodrigo-Calvo, Naiara Vega, Ricardo López Del Campo, Rafael Parra-Medina, Tarek Ajami, Antonio Martínez, Oscar Reig, Maria J Ribal, Juan Manuel Corral-Molina, Pedro Jares, Jaume Ordi, Natalia Rakislova
Department of Pathology, Hospital Clínic of Barcelona, University of Barcelona, 08036 Barcelona, Spain., Institute of Pathology, Lausanne University Hospital, Lausanne University, 1011 Lausanne, Switzerland., Department of Pathology, Research Institute, Fundación Universitaria de Ciencias de la Salud, Bogota 111221, Colombia., Uro-Oncology Unit, Hospital Clínic of Barcelona, University of Barcelona, 08036 Barcelona, Spain., Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.