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
References
Sep 20, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Muralidhar BeeramEric K Rowinsky
Feb 28, 2008·Current Opinion in Oncology·Leslie A FecherKeith T Flaherty
Feb 10, 2010·Cell·Sonja J HeidornRichard Marais
Dec 31, 2010·Current Opinion in Oncology·Caroline RobertChristine Mateus
Jun 7, 2011·The New England Journal of Medicine·Paul B ChapmanUNKNOWN BRIM-3 Study Group
Jun 24, 2011·Journal of Applied Genetics·Chandra Shekhar PareekAndrzej Tretyn
Nov 10, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Patrick A OberholzerLevi A Garraway
Jan 20, 2012·The New England Journal of Medicine·Fei SuRichard Marais
May 23, 2012·Journal of the American Academy of Dermatology·Emily Y ChuMisha Rosenbach
Jun 9, 2012·Pharmacogenomics·Joseph HensonZemin Ning
Jun 26, 2012·Pigment Cell & Melanoma Research·Rachael AnforthPablo Fernandez-Peñas
Jun 28, 2012·Lancet·Axel HauschildPaul B Chapman
Jul 19, 2012·The British Journal of Dermatology·R M AnforthP Fernandez-Peñas
Sep 4, 2012·Journal of the American Academy of Dermatology·Kevin P BoydLauren C Hughey
Jul 3, 2013·The Journal of Molecular Diagnostics : JMD·Rajesh R SinghRajyalakshmi Luthra
Nov 7, 2013·ELife·Harina VinKenneth Y Tsai
Feb 14, 2014·Cancer Research·Matthew HolderfieldDarrin Stuart
Citations
Jan 28, 2017·The British Journal of Dermatology·J H WuS K Tyring
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
Dec 3, 2016·The Prostate·Nima C EmamiJeffry P Simko
Apr 26, 2020·International Journal of Molecular Sciences·Roberto Corchado-CobosJavier Cañueto
Jun 3, 2021·Cancers·Elizabeth L ThompsonLaura J Niedernhofer