NOTCH1 mutations occur early during cutaneous squamous cell carcinogenesis

DSpace/Manakin Repository

NOTCH1 mutations occur early during cutaneous squamous cell carcinogenesis

Citable link to this page


Title: NOTCH1 mutations occur early during cutaneous squamous cell carcinogenesis
Author: South, Andrew P; Purdie, Karin J; Watt, Stephen A; Haldenby, Sam; den Breems, Nicoline; Dimon, Michelle; Arron, Sarah T; Kluk, Michael J; Aster, Jon C; McHugh, Angela; Xue, Dylan J; Dayal, Jasbani HS; Robinson, Kim S; Rizvi, SM Hasan; Proby, Charlotte M; Harwood, Catherine A; Leigh, Irene M

Note: Order does not necessarily reflect citation order of authors.

Citation: South, A. P., K. J. Purdie, S. A. Watt, S. Haldenby, N. den Breems, M. Dimon, S. T. Arron, et al. 2014. “NOTCH1 mutations occur early during cutaneous squamous cell carcinogenesis.” The Journal of investigative dermatology 134 (10): 2630-2638. doi:10.1038/jid.2014.154.
Full Text & Related Files:
Abstract: Cutaneous SCC (cSCC) is the most frequent 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 132 sporadic cSCC, 39 squamoproliferative lesions and cSCC arising in patients receiving the BRAF inhibitor vemurafenib, as well as 10 normal skin samples to identify significant 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 cSCC and regions of NOTCH1 loss or down-regulation are frequently observed in normal looking skin. Our data indicate that NOTCH1 acts as a gatekeeper in human cSCC.
Published Version: doi:10.1038/jid.2014.154
Other Sources:
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at
Citable link to this page:
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)


Search DASH

Advanced Search