The molecular cartography of malignant and benign sebaceous tumours
Sebaceous tumours (STs) are rare skin appendage tumours and include benign sebaceous adenoma (SA) and sebaceoma (SM), malignant extra-ocular sebaceous carcinoma (SC-E) and peri-ocular sebaceous carcinoma (SC-O). Here, an extensive worldwide collection of 286 tumours is deeply characterised, revealing a propensity to develop in the context of a high tumour mutational burden (except in SC-O) which is most frequently associated with mismatch repair deficiency (dMMR), followed by UV-induced damage, POLE/POLD1 mutations, and AID/APOBEC activation signatures. Biallelic TP53 inactivation with concomitant ZNF750 and/or RB1 mutation is seen in SC-E/SC-O. Amplification of 8q (including MYC) is related to SC-O, while amplification of 1q21.3 (including HRNR) and chromosome 20 are shared by SC-O and SC-E, as is deletion of 13q14.3 (where RB1 resides). The most frequently mutated gene is NOTCH1. Extensive fusion gene, expression and molecular cluster analyses provide a molecular portrait of this rare and enigmatic tumour type.
Authors
- Prashant Gupta (ORCID: https://orcid.org/0000-0003-4211-9125)
- Oscar M. Rueda (ORCID: https://orcid.org/0000-0003-0008-4884)
- Anca Oniscu
- Oliver Cast (ORCID: https://orcid.org/0000-0002-5880-7726)
- Thomas Brenn (ORCID: https://orcid.org/0000-0002-0089-0352)
- Tobi Alegbe (ORCID: https://orcid.org/0000-0003-1622-0502)
- Masakazu Fujimoto (ORCID: https://orcid.org/0000-0002-0575-6507)
- Mark J. Arends (ORCID: https://orcid.org/0000-0002-6826-8770)
- Kun Wang (ORCID: https://orcid.org/0000-0001-8923-8557)
- Martin Del Castillo Velasco‐Herrera (ORCID: https://orcid.org/0000-0001-5956-0211)
- Louise van der Weyden (ORCID: https://orcid.org/0000-0002-0645-1879)
- Ashray Gunjur (ORCID: https://orcid.org/0000-0001-9713-1872)
- A. Stratigos
- Katharina Wiedemeyer (ORCID: https://orcid.org/0000-0002-0754-2393)
- Ingrid Ferreira (ORCID: https://orcid.org/0000-0002-4321-5250)
- Jacqueline Marcia Boccacino (ORCID: https://orcid.org/0000-0001-6813-5217)
- Eytan Ruppin (ORCID: https://orcid.org/0000-0002-7862-3940)
- Kim Wong (ORCID: https://orcid.org/0000-0002-0984-1477)
- Ian M. Frayling (ORCID: https://orcid.org/0000-0002-3420-0794)
- Helen Caldwell (ORCID: https://orcid.org/0000-0002-5531-6593)
- Ishan Mehta (ORCID: https://orcid.org/0000-0002-2939-917X)
- Victoria Harle (ORCID: https://orcid.org/0000-0002-5953-4766)
- Pieter Demetter (ORCID: https://orcid.org/0000-0001-7981-4645)
- Kaori Azuma Koga (ORCID: https://orcid.org/0000-0002-5057-4120)
- Sahil Sahni (ORCID: https://orcid.org/0009-0006-4678-3903)
- David J. Adams (ORCID: https://orcid.org/0000-0001-9490-0306)
- I. Matzusaki
Institutions
- European Bioinformatics Institute (GB)
- Université Libre de Bruxelles (BE)
- Karolinska University Hospital (SE)
- University of Illinois Urbana-Champaign (US)
- University of Calgary (CA)
- Wakayama Medical University (JP)
- National and Kapodistrian University of Athens (GR)
- University of Cambridge (GB)
- University of Michigan (US)
- Institut Jules Bordet (BE)
- Wellcome Sanger Institute (GB)
- Edinburgh Cancer Research (GB)
- Open Targets (GB)
- Cancer Research UK Cambridge Center (GB)
- Office of the Director (US)
- Fukuoka University Hospital (JP)
- Andreas Sygros Hospital (GR)
- MRC Biostatistics Unit (GB)
- National Cancer Institute (US)
- Centre d'Enseignement et de Recherches des Industries Alimentaires et Chimiques (BE)
- Kyoto University Hospital (JP)
- Cardiff University (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-19
- DOI
- https://doi.org/10.1038/s41467-025-66584-0
- Primary Topic
- Nonmelanoma Skin Cancer Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00