Intra-patient Heterogeneity of BRAF and NRAS Molecular Alterations in Primary Melanoma and Metastases

• Main Authors: Cristina Pellegrini, Ludovica Cardelli, Marina De Padova, Lucia Di Nardo, Valeria Ciciarelli, Tea Rocco, Gianluca Cipolloni, Marco Clementi, Alessio Cortellini, Alessandra Ventura, Pietro Leocata, Maria Concetta Fargnoli
• Format: Article
• Language: English
• Published: Society for Publication of Acta Dermato-Venereologica 2020-01-01
• Series: Acta Dermato-Venereologica
• Subjects: melanoma; metastases; braf; nras; c-kit; heterogeneity
• Online Access: https://www.medicaljournals.se/jadv/content/html/10.2340/00015555-3382

Mutations in MAPK signalling genes are driver events in melanoma, and have therapeutic relevance in the metastatic and adjuvant setting. This study evaluated the intra-patient heterogeneity of BRAF, NRAS and c-KIT mutational status between 30 primary melanomas and 39 related metastases, using molecular analysis and immunohistochemistry. BRAF mutations were identified in 46.7% of primary melanomas and 48.7% of metastases and NRAS mutations in 20% and 25.6%, respectively. Intra-patient heterogeneity was detected in 13.3% of patients for both BRAF and NRAS genes and was not associated with clinico-pathological characteristics of melanomas or metastases. High consistency was observed between immunostaining and molecular methods for BRAFV600E (k = 0.90; p < 0.001) and NRASQ61R (k = 0.87; p < 0.001). These findings demonstrate a relevant intra-patient heterogeneity between primary and metastatic lesions that is independent of clinical variables and methodological approach.