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Cell of origin and mutation pattern define three clinically distinct classes of sebaceous carcinoma.
- Source :
-
Nature communications [Nat Commun] 2018 May 14; Vol. 9 (1), pp. 1894. Date of Electronic Publication: 2018 May 14. - Publication Year :
- 2018
-
Abstract
- Sebaceous carcinomas (SeC) are cutaneous malignancies that, in rare cases, metastasize and prove fatal. Here we report whole-exome sequencing on 32 SeC, revealing distinct mutational classes that explain both cancer ontogeny and clinical course. A UV-damage signature predominates in 10/32 samples, while nine show microsatellite instability (MSI) profiles. UV-damage SeC exhibited poorly differentiated, infiltrative histopathology compared to MSI signature SeC (pā=ā0.003), features previously associated with dissemination. Moreover, UV-damage SeC transcriptomes and anatomic distribution closely resemble those of cutaneous squamous cell carcinomas (SCC), implicating sun-exposed keratinocytes as a cell of origin. Like SCC, this UV-damage subclass harbors a high somatic mutation burden with >50 mutations per Mb, predicting immunotherapeutic response. In contrast, ocular SeC acquires far fewer mutations without a dominant signature, but show frequent truncations in the ZNF750 epidermal differentiation regulator. Our data exemplify how different mutational processes convergently drive histopathologically related but clinically distinct cancers.
- Subjects :
- Carcinoma, Squamous Cell classification
Carcinoma, Squamous Cell diagnosis
Carcinoma, Squamous Cell pathology
DNA Mutational Analysis
Diagnosis, Differential
Exome
Eye Neoplasms classification
Eye Neoplasms diagnosis
Eye Neoplasms pathology
Humans
Keratinocytes metabolism
Keratinocytes pathology
Keratinocytes radiation effects
Microsatellite Repeats
Sebaceous Gland Neoplasms classification
Sebaceous Gland Neoplasms diagnosis
Sebaceous Gland Neoplasms pathology
Skin Neoplasms classification
Skin Neoplasms diagnosis
Skin Neoplasms etiology
Terminology as Topic
Transcriptome
Ultraviolet Rays adverse effects
Exome Sequencing
Carcinoma, Squamous Cell genetics
Eye Neoplasms genetics
Microsatellite Instability
Mutation
Sebaceous Gland Neoplasms genetics
Skin Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 29760388
- Full Text :
- https://doi.org/10.1038/s41467-018-04008-y