Clinicopathologic and molecular characterization of melanomas mutated for CTNNB1 and MAPK

Wnt/beta-catenin signaling plays crucial roles in melanocyte biology and may be implicated in melanoma progression. In this study, we retrospectively examined a real-life cohort of melanomas mutated for beta-catenin (CTNNB1), in association or not with a MAPK mutation (of BRAF or NRAS), and analyzed their clinical, histopathological, and molecular characteristics. Our results indicate that, regardless of the presence of a concurrent MAPK mutation, CTNNB1(mut) cutaneous primary melanomas display more proliferative hallmarks (increased Breslow thickness, mitotic index, and ulceration) than their CTNNB1 wild-type counterparts. Accordingly, they often progress to the metastatic stage. Furthermore, concurrent CTNNB1 and MAPK mutations do not necessarily confer a deep penetrating nevi phenotype. Altogether, this study provides evidence that CTNNB1 mutations in melanomas are associated with specific clinical and pathological features.

Automated summary

The study suggests that CTNNB1 mutations in melanomas are associated with increased proliferative characteristics and progression to metastatic stage, regardless of the concurrent presence of MAPK mutations. Additionally, the co-occurrence of CTNNB1 and MAPK mutations does not necessarily result in a deep penetrating nevi phenotype.