The genomic landscape of cutaneous squamous carcinoma identifies drivers and a novel mutational signature associated with azathioprine exposure


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Gareth Inman1,Jun Wang2,Ai Nagano2,Ludmil Alexandrov3,Karin Purdie4,Richard Taylor1,Victoria Sherwood1,Jason Thomson4,Sarah Hogan4,Lindsay Spender1,Andrew South5,Michael Stratton6,Claude Chellala2,Catherine Harwood7,Charlotte Proby1,Irene Leigh4
1University of Dundee,2Barts Cancer Institute,3UCSD,4QMUL,5Thomas Jefferson University,6Wellcome Trust Sanger Institute,7Qmul

Abstract

Background

Cutaneous squamous cell carcinoma is increasing year on year and exhibits a high mutational burden of 50 mutations per megabase. Deciphering the drivers of disease progression remains a challenge.

Method

We performed whole exome sequencing on 40 primary cutaneous SCCs isolated form immunocompetent and immunosuppressed patients. We employed mutational analysis programmes to identify drivers and mutational signatures.

Results

We identified putative driver genes, pathways and processes associated with cSCC formation and progression and a novel mutational signature associated with chronic azathioprine exposure.

Conclusion

This study has identified azathioprine as a potential mutagen in cSCC and novel driver genes and pathways associated with disease progression.