NOTCH1 mutations occur early during cutaneous squamous cell carcinogenesis Academic Article uri icon


MeSH Major

  • Carcinogenesis
  • Carcinoma, Squamous Cell
  • Mutation
  • Receptor, Notch1
  • Signal Transduction
  • Skin Neoplasms


  • Cutaneous SCC (cSCC) is the most frequently occuring skin cancer with metastatic potential and can manifest rapidly as a common side effect in patients receiving systemic kinase inhibitors. Here, we use massively parallel exome and targeted level sequencing of 132 sporadic cSCCs and of 39 squamoproliferative lesions and cSCCs arising in patients receiving the BRAF inhibitor vemurafenib, as well as 10 normal skin samples, to identify NOTCH1 mutation as an early event in squamous cell carcinogenesis. Bisected vemurafenib-induced lesions revealed surprising heterogeneity with different activating HRAS and NOTCH1 mutations identified in two halves of the same cSCC, suggesting polyclonal origin. Immunohistochemical analysis using an antibody specific to nuclear NOTCH1 correlates with mutation status in sporadic cSCCs, and regions of NOTCH1 loss or downregulation are frequently observed in normal-looking skin. Our data indicate that NOTCH1 acts as a gatekeeper in human cSCC.

publication date

  • January 2014



  • Academic Article



  • eng

PubMed Central ID

  • PMC4753672

Digital Object Identifier (DOI)

  • 10.1038/jid.2014.154

PubMed ID

  • 24662767

Additional Document Info

start page

  • 2630

end page

  • 8


  • 134


  • 10