GPS1 Exon 9 Mutations Represent a Rare Genetic Event in Penile Squamous Cell Carcinoma Pathogenesis

Tögel L, Elsner F, Wendler O, Giedl J, Gaisa NT, Richter G, Campean V, Burger M, Wullich B, Bertz S, Hartmann A, Stöhr R (2026)

Publication Type: Journal article

Publication year: 2026

Journal

International Journal of Molecular Sciences MDPI

Book Volume: 27

Article Number: 2460

Journal Issue: 5

DOI: 10.3390/ijms27052460

Abstract

Penile squamous cell carcinoma (PSCC) is rare, but a biologically aggressive malignancy. Recent comprehensive genomic profiling (CPG) efforts revealed the underlying genomic landscape of PSCC, identifying TP53, TERT, CDKN2A, PIK3CA, NOTCH1, and FAT1 as frequently altered genes with potential roles in penile oncogenesis. In addition, recurrent mutations encoded in the GPS1 gene have been observed in 7.4% of cases in a particular PSCC cohort. Functional studies demonstrated loss of function due to GPS1 Exon 9 missense mutations, proposing a possible role for these alterations as oncogenic driver events in PSCC. However, no other study confirmed the occurrence of GPS1 gene mutations in PSCC. To elucidate the biological function of GPS1 exon 9 mutations in PSCC pathogenesis, we utilized a comprehensive in-house cohort of 106 PSCC cases to explore their frequency and occurrence. Albeit, the previously reported GPS1 mutations p.D382H and p.M384I were not observed in this large cohort of PSCC cases; this analysis, however, revealed two novel GPS1 alterations in exon 9 in two (1.9%) of the analyzed cases: p.S372F (c.1115C>T) and p.A375D (c.1124C>A). This observation suggests that GPS1 exon 9 sequence is a target of genetic alteration during PSCC pathogenesis. However, the non-recurrent nature of these alterations indicates that they are unlikely to represent oncogenic drivers in this disease.

Authors with CRIS profile

Lars Tögel Institute of Pathology Felix Elsner Institute of Pathology Olaf Wendler Department of Otorhinolaryngology – Head and Neck Surgery (HNO-Klinik) Bernd Wullich Lehrstuhl für Urologie Simone Bertz Institute of Pathology Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Robert Stöhr Institute of Pathology

Involved external institutions

Universitätsklinikum Ulm DE Germany (DE) Pathologie Ansbach DE Germany (DE) Universität Regensburg DE Germany (DE)

How to cite

APA:

Tögel, L., Elsner, F., Wendler, O., Giedl, J., Gaisa, N.T., Richter, G.,... Stöhr, R. (2026). GPS1 Exon 9 Mutations Represent a Rare Genetic Event in Penile Squamous Cell Carcinoma Pathogenesis. International Journal of Molecular Sciences, 27(5). https://doi.org/10.3390/ijms27052460

MLA:

Tögel, Lars, et al. "GPS1 Exon 9 Mutations Represent a Rare Genetic Event in Penile Squamous Cell Carcinoma Pathogenesis." International Journal of Molecular Sciences 27.5 (2026).

BibTeX: Download