Mutational analysis of cutaneous squamous cell carcinomas and verrucal keratosis in patients taking BRAF inhibitors.
B-RAF inhibitors (BRAFi) have been shown to improve rates of overall and progression-free survival in patients with stage IV metastatic melanoma positive for the BRAF V600E mutation. However, the main drawback is the development of verrucal keratosis (hyperkeratotic papules with verruca-like characteristics with benign histological findings) and cutaneous squamous cell carcinomas (cuSCC). We have found upstream mutations in RAS as well as PIK3CA in both verrucal keratosis and cuSCC. This suggests that verrucal keratosis is an early clinical presentation of cuSCC in patients on BRAFi.
Department of Dermatology, Westmead Hospital, Sydney, NSW, Australia. rachael.anforth@sydney.edu.au
Rachael
R
Anforth
Varsha
V
Tembe
Tatiana
T
Blumetti
Pablo
P
Fernandez-Peñas
D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D006801:Humans; D007642:Keratosis / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D014860:Warts / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics / Q000473:pathology
D047428:Protein Kinase Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf