Mutational analysis of cutaneous squamous cell carcinomas and verrucal keratosis in patients taking BRAF inhibitors

Pigment Cell Melanoma Res. 2012 Sep;25(5):569-72. doi: 10.1111/j.1755-148X.2012.01031.x. Epub 2012 Aug 6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Carcinoma, Squamous Cell / chemically induced*
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Class I Phosphatidylinositol 3-Kinases
  • DNA Mutational Analysis
  • Exons / genetics
  • Humans
  • Keratosis / chemically induced*
  • Keratosis / enzymology
  • Keratosis / genetics
  • Keratosis / pathology
  • Molecular Sequence Data
  • Phosphatidylinositol 3-Kinases / genetics
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Proto-Oncogene Proteins B-raf / metabolism
  • Skin Neoplasms / chemically induced*
  • Skin Neoplasms / enzymology
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology
  • Warts / chemically induced*
  • Warts / enzymology
  • Warts / genetics
  • Warts / pathology

Substances

  • Protein Kinase Inhibitors
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf