Subtype-Specific Analyses Reveal Infiltrative Basal Cell Carcinomas Are Highly Interactive with their Environment

Rehan Villani, Valentine Murigneux, Josue Alexis, Seen Ling Sim, Michael Wagels, Nicholas Saunders, H. Peter Soyer, Laurent Parmentier, Sergey Nikolaev, J. Lynn Fink, Edwige Roy, Kiarash Khosrotehrani

Résultats de recherche: Contribution à un journalArticleRevue par des pairs

11 Citations (Scopus)

Résumé

Little is known regarding the molecular differences between basal cell carcinoma (BCC) subtypes, despite clearly distinct phenotypes and clinical outcomes. In particular, infiltrative BCCs have poorer clinical outcomes in terms of response to therapy and propensity for dissemination. In this project, we aimed to use exome sequencing and RNA sequencing to identify somatic mutations and molecular pathways leading to infiltrative BCCs. Using whole-exome sequencing of 36 BCC samples (eight infiltrative) combined with previously reported exome data (58 samples), we determine that infiltrative BCCs do not contain a distinct somatic variant profile and carry classical UV-induced mutational signatures. RNA sequencing on both datasets revealed key differentially expressed genes, such as POSTN and WISP1, suggesting increased integrin and Wnt signaling. Immunostaining for periostin and WISP1 clearly distinguished infiltrative BCCs, and nuclear β-catenin staining patterns further validated the resulting increase in Wnt signaling in infiltrative BCCs. Of significant interest, in BCCs with mixed morphology, infiltrative areas expressed WISP1, whereas nodular areas did not, supporting a continuum between subtypes. In conclusion, infiltrative BCCs do not differ in their genomic alteration in terms of initiating mutations. They display a specific type of interaction with the extracellular matrix environment regulating Wnt signaling.

langue originaleAnglais
Pages (de - à)2380-2390
Nombre de pages11
journalJournal of Investigative Dermatology
Volume141
Numéro de publication10
Les DOIs
étatPublié - 1 oct. 2021
Modification externeOui

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