title: High incidence of naevi-associated BRAF wild-type melanoma and dysplastic naevi under treatment with the class I BRAF inhibitor vemurafenib.
abstract: There is growing evidence that not only malign keratinocytic but also melanocytic tumours can arise during treatment with vemurafenib. During an on-going early access trial, 13 patients harbouring a BRAF-V600E mutation received vemurafenib (Zelboraf®) 960 mg twice daily to test the safety, tolerability, efficacy and response rate for advanced melanoma. Clinically or dermatoscopically suspicious cutaneous tumours under treatment with vemurafenib were excised. The BRAF-V600E status of confirmed new primary melanoma and dysplastic naevi was tested using a genetic mutation assay and immunohistochemistry. Four of the 13 patients (31%) developed 4 new naevi-associated malignant melanomas and 5 dysplastic naevi between 6 weeks and 6 months after the start of treatment. With the exception of one in situ melanoma, all tumours were BRAF wild-type. Immunohistochemistry revealed increased expression of ERK, pERK and active Rac1-GTP in the naevi-associated melanoma and dysplastic naevi. Careful and continuous skin examination, including dermoscopy, appears to be required during treatment with vemurafenib.
authors: Department of Dermatology and Venereology, Otto-von-Guericke University, Leipziger Str. 44, DE-39120 Magdeburg, Germany.
authors: Daniela
authors: D
authors: Göppner
authors: Jan
authors: J
authors: Müller
authors: Sabine
authors: S
authors: Krüger
authors: Ingolf
authors: I
authors: Franke
authors: Harald
authors: H
authors: Gollnick
authors: Sven R
authors: SR
authors: Quist
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000556:secondary; D004416:Dysplastic Nevus Syndrome / Q000235:genetics / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000009:adverse effects*; D008175:Lung Neoplasms / Q000556:secondary; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D010446:Peptide Fragments / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D013449:Sulfonamides / Q000009:adverse effects*; D000077484:Vemurafenib; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D010446:Peptide Fragments; C403751:Rac1 GTP-binding protein (17-32); D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048049:Extracellular Signal-Regulated MAP Kinases; D020830:rac1 GTP-Binding Protein