THE GENOMIC LANDSCAPE OF ACTINIC KERATOSIS
Actinic keratoses (AK) are lesions of epidermal keratinocyte dysplasia and are precursors for invasive cutaneous squamous cell carcinoma (CSCC). Identifying the specific genomic alterations driving progression from normal skin-AK-invasive CSCC is challenging due to the massive ultraviolet radiation-induced mutational burden characteristic at all stages of this progression. Here, we report the largest AK whole exome sequencing study to date and perform mutational signature and candidate driver gene analysis on these lesions. We demonstrate in 37 AK, from both immunosuppressed and immunocompetent patients, that there are significant similarities to CSCC in terms of mutational burden, copy number alterations, mutational signatures and patterns of driver gene mutations. We identify 44 significantly mutated AK driver genes and confirm that these genes are similarly altered in CSCC. We identify the azathioprine mutational signature in all AK from patients exposed to the drug, providing further evidence for its role in keratinocyte carcinogenesis. CSCC differ from AK in having higher levels of intra-sample heterogeneity. Alterations in signaling pathways also differ, with immune-related signaling and TGF-β signaling significantly more mutated in CSCC. Integrating our findings with independent gene expression datasets confirms that dysregulated TGF-β signaling may represent an important event in AK-CSCC progression.
- 74 samples
- DAC: EGAC00001001926
- Technology: Illumina HiSeq 2500
THE GENOMIC LANDSCAPE OF ACTINIC KERATOSIS
European Genome-Phenome Archive c/o European Bioinformatics Institute Wellcome Trust Genome Campus Hinxton Cambridge CB10 1SD United Kingdom To whom it may concern, This document refers to the study, EGAS00001004243, which have been submitted to the European Genome Archive (EGA) for the restricted access by legitimate academic institutions that have agreed to comply with the terms of a Data Access Agreement drafted by Cutaneous SCC genomic landscape project (UK) EGAC00001000516. There are a number of steps that a researcher must take to obtain access to this data and the process is overseen by our Data Access Committee, called Cutaneous SCC genomic landscape project (UK), contact Dr Gareth Inman, email g.j.inman@dundee.ac.uk or Prof Irene Leigh, email I.M.Leigh@dundee.ac.uk Please be advised that Dr Jun Wang, j.a.wang@qmul.ac.uk, is authorized to upload data to the EGA for archiving and distribution as part of your submission process, which will enable approved researchers to have encrypted access to the data. We can confirm that this submission is consistent with the informed consent of the participants of the study or has been granted ethical approval and is in accordance with the applicable laws and regulations. Yours Sincerely, Gareth Inman Irene Leigh Division of Cancer Research Jacqui Wood Cancer Centre University of Dundee James Arrott Drive Ninewells Hospital And Medical School Dundee DD1 9SY
Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.
| Study ID | Study Title | Study Type |
|---|---|---|
| EGAS00001004243 | Other |
This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.