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The mutational landscape of skin tumours in CYLD cutaneous syndrome determined

Patients with germline mutations in CYLD can develop hundreds of benign skin tumours called cylindromas. The development of multiple tumours within a single patient at sun-protected and sun-exposed sites, varying tumour histological patterns and grades of malignancy allow for the testing of several genetic hypothesis in relation to cutaneous carcinogenesis. By adopting the unprecedented approach of whole genome sequencing of multiple benign skin tumours within individuals in multigenerational families, we set out to study the impact of mutational diversity on models such as multistep carcinogenesis as well as non-sequential carcinogenesis. Using non-negative matrix factorisation (NMF) to discover mutational signatures, we found distinct mutational signatures in identical benign tumours (N=2 patients; n=11 tumours) at sun exposed and sun protected skin tumours within a mother and her daughter. We found recurrent mutations in epigenetic modifying genes in CCS tumours which are known to have an oncogenic dependency on Wnt signalling. We also demonstrate that cutaneous tumours that metastasize to the lung carry a a UV signature, supporting the origin from the skin. Distinct malignant tumours, such as BCC and malignant spiradenocarcinoma carried unique driver mutations. These findings add new dimensions to the existing paradigms of UV-induced skin cancer and highlight the utility of studying rare disease to gain novel insights into genetic mechanisms of tumour formation.

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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
EGAS00001002521 Cancer Genomics

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.

ID File Type Size Located in
EGAF00002211125 cram 5.4 GB
EGAF00002211126 cram 5.4 GB
EGAF00002211127 cram 5.7 GB
EGAF00002211128 cram 5.9 GB
EGAF00002211129 cram 5.5 GB
EGAF00002217137 cram 7.4 GB
EGAF00002217138 cram 7.5 GB
EGAF00002217139 cram 7.6 GB
EGAF00002217140 cram 7.8 GB
EGAF00002217141 cram 7.6 GB
EGAF00002217142 cram 7.9 GB
EGAF00002217143 cram 7.7 GB
EGAF00002217144 cram 8.1 GB
EGAF00002217145 cram 8.7 GB
EGAF00002217146 cram 8.9 GB
EGAF00002217147 cram 8.9 GB
EGAF00002217148 cram 9.2 GB
EGAF00002217149 cram 7.4 GB
EGAF00002217150 cram 7.6 GB
EGAF00002217151 cram 7.5 GB
EGAF00002217152 cram 7.8 GB
EGAF00002217291 cram 5.4 GB
EGAF00002217292 cram 5.5 GB
EGAF00002217293 cram 5.6 GB
EGAF00002217294 cram 5.8 GB
EGAF00002217295 cram 5.4 GB
EGAF00002217297 cram 5.4 GB
EGAF00002217325 cram 5.4 GB
EGAF00002217326 cram 5.6 GB
EGAF00002217327 cram 5.8 GB
EGAF00002217328 cram 5.4 GB
EGAF00002217330 cram 5.3 GB
EGAF00002217331 cram 5.4 GB
EGAF00002217332 cram 5.5 GB
EGAF00002217333 cram 5.7 GB
EGAF00002217334 cram 5.3 GB
EGAF00002217336 cram 5.2 GB
EGAF00002217337 cram 5.2 GB
EGAF00002217338 cram 5.4 GB
EGAF00002217339 cram 5.6 GB
EGAF00002217340 cram 5.2 GB
EGAF00002217342 cram 5.2 GB
EGAF00002217343 cram 5.3 GB
EGAF00002217344 cram 5.5 GB
EGAF00002217345 cram 5.6 GB
EGAF00002217346 cram 5.2 GB
EGAF00002217347 cram 5.3 GB
EGAF00002217348 cram 5.3 GB
EGAF00002217350 cram 5.3 GB
EGAF00002217352 cram 5.4 GB
EGAF00002217353 cram 5.4 GB
EGAF00002217383 cram 5.3 GB
EGAF00002217385 cram 5.3 GB
EGAF00002217387 cram 5.4 GB
EGAF00002217388 cram 5.2 GB
EGAF00002217389 cram 5.1 GB
EGAF00002217391 cram 5.1 GB
EGAF00002217393 cram 5.3 GB
EGAF00002217394 cram 5.1 GB
EGAF00002217395 cram 5.2 GB
EGAF00002217397 cram 5.1 GB
EGAF00002217399 cram 5.2 GB
EGAF00002217400 cram 5.0 GB
EGAF00002217401 cram 5.1 GB
EGAF00002217403 cram 5.0 GB
EGAF00002217405 cram 5.1 GB
EGAF00002217406 cram 5.1 GB
EGAF00002217409 cram 5.0 GB
EGAF00002217411 cram 5.2 GB
69 Files (410.6 GB)