Document Type

Article

Publication Date

12-1-2018

Comments

This article has been peer reviewed. It is the author’s final published version in Nature Communications, Volume 9, Issue 1, December 2018, Article number 3667.

The published version is available at https://doi.org/10.1038/s41467-018-06027-1. Copyright © Inman et al.

Abstract

Cutaneous squamous cell carcinoma (cSCC) has a high tumour mutational burden (50 mutations per megabase DNA pair). Here, we combine whole-exome analyses from 40 primary cSCC tumours, comprising 20 well-differentiated and 20 moderately/poorly differentiated tumours, with accompanying clinical data from a longitudinal study of immunosuppressed and immunocompetent patients and integrate this analysis with independent gene expression studies. We identify commonly mutated genes, copy number changes and altered pathways and processes. Comparisons with tumour differentiation status suggest events which may drive disease progression. Mutational signature analysis reveals the presence of a novel signature (signature 32), whose incidence correlates with chronic exposure to the immunosuppressive drug azathioprine. Characterisation of a panel of 15 cSCC tumour-derived cell lines reveals that they accurately reflect the mutational signatures and genomic alterations of primary tumours and provide a valuable resource for the validation of tumour drivers and therapeutic targets.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

30202019

Language

English

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