Mutational Analysis of BRAF Inhibitor-Associated Squamoproliferative Lesions

The Journal of Molecular Diagnostics : JMD
Britt ClynickNathan T Harvey

Abstract

In recent years, there has been increasing use of BRAF-inhibiting drugs for the treatment of various malignancies, including melanoma. However, these agents are associated with the development of other nonmelanoma skin lesions, in particular squamoproliferative lesions such as keratoacanthomas (KAs), squamous cell carcinomas, and BRAF inhibitor-associated verrucous keratoses. The molecular pathogenesis of these lesions is of interest, not only for therapeutic reasons, but also for the insight it might provide into the development of similar lesions in a sporadic setting. We used next-generation sequencing to compare the mutational profiles of lesions after treatment with a BRAF inhibitor, with similar lesions arising sporadically. HRAS mutations were common among the BRAF inhibitor-induced lesions, being identified in 56%, compared with 14% of lesions in the sporadic group (P = 0.002). Thus, despite similar histomorphological appearances, the underlying molecular mechanisms may be different. In addition, within the BRAF inhibitor-associated group, the lesions designated as KAs and BRAF inhibitor-associated verrucous keratoses had a similar mutational profile (mutations in PIK3CA, APC, and HRAS), which was distinct to that seen ...Continue Reading

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Citations

Nov 21, 2019·Journal of the European Academy of Dermatology and Venereology : JEADV·L Di NardoK Peris
Jul 25, 2017·The Journal of Dermatology·Yoshio NakamuraNaoya Yamazaki
Aug 18, 2016·The American Journal of Dermatopathology·William D LonghurstMeg R Gerstenblith
Apr 26, 2020·International Journal of Molecular Sciences·Roberto Corchado-CobosJavier Cañueto

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