Cutaneous Epithelial Tumors Induced by Vemurafenib Involve the MAPK and Pi3KCA Pathways but Not HPV nor HPyV Viral Infection

Eric Frouin (1) , Bernard Guillot (1, 2) , Marion Larrieux (3) , Ariane Tempier (1) , Nathalie Boulle (3, 2) , Vincent Foulongne (2, 3) , Céline Girard (2) , Valérie Costes (3, 2) , Jérôme Solassol (3, 4)

1 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
2 Pathogénèse et contrôle des infections chroniques (PCCI)
3 Service de Biopathologie [CHRU Montpellier]
4 IRCM - U896 Inserm - UM1 - Institut de recherche en cancérologie de Montpellier

The inhibitors of mutant BRAF that are used to treat metastatic melanoma induce squamoproliferative lesions. We conducted a prospective histopathological and molecular study on 27 skin lesions from 12 patients treated with vemurafenib. Mutation hot spots in HRAS, NRAS, KRAS, BRAF, and Pi3KCA were screened. HPV and HPyV infection status were also determined. The lesions consisted of 19 verrucal papillomas, 1 keratoacanthoma and 7 squamous cell carcinomas. No mutations were found within BRAF and NRAS. KRAS, HRAS, and Pi3KCA oncogenic mutations were found in 10 (83.3%), 7 (58.3%), and 4 (33.3%) patients respectively; however, these mutations were not consistent within all tumors of a given patient. Pi3KCA mutation was always associated with a mutation in HRAS. Finally, no correlation was found between the mutated gene or type of mutation and the type of cutaneous tumor or clinical response to vemurafenib. P16 protein level was not indicative of HPV infection. HPV was detected in only two lesions. Two cases had MCPyV, and one had HPyV7. In conclusion, neither HPV nor HPyV seem to be involved in the development of squamoproliferative lesions induced by verumafenib. By contrast, HRAS and KRAS play a predominant role in the physiopathology of these tumors.

Domaines: Sciences du Vivant [q-bio]; Cancer

Eric Frouin, Bernard Guillot, Marion Larrieux, Ariane Tempier, Nathalie Boulle, et al.. Cutaneous Epithelial Tumors Induced by Vemurafenib Involve the MAPK and Pi3KCA Pathways but Not HPV nor HPyV Viral Infection. PLoS ONE, 2014, 9 (10), pp.e110478. ⟨10.1371/journal.pone.0110478⟩. ⟨hal-02090991⟩