Cell of origin and mutation pattern define three clinically distinct classes of sebaceous carcinoma

Media type: E-Article
Title: Cell of origin and mutation pattern define three clinically distinct classes of sebaceous carcinoma
Contributor: North, Jeffrey P.; Golovato, Justin; Vaske, Charles J.; Sanborn, J. Zachary; Nguyen, Andrew; Wu, Wei; Goode, Benjamin; Stevers, Meredith; McMullen, Kevin; Perez White, Bethany E.; Collisson, Eric A.; Bloomer, Michele; Solomon, David A.; Benz, Stephen C.; Cho, Raymond J.
imprint: Springer Science and Business Media LLC, 2018
Published in: Nature Communications
Language: English
DOI: 10.1038/s41467-018-04008-y
ISSN: 2041-1723
Origination:
Footnote:
Description: <jats:title>Abstract</jats:title><jats:p>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 (<jats:italic>p</jats:italic> = 0.003), 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.</jats:p>
Access State: Open Access

Search in field:

Recently searched for: