The molecular cartography of malignant and benign sebaceous tumours

作者：Ingrid Ferreira, Oscar M. Rueda, Louise van der Weyden, Sahil Sahni, Oliver Cast, Kim Wong, Martin Del Castillo Velasco‐Herrera, Helen Caldwell, Jacqueline Marcia Boccacino, Tobi Alegbe, Ishan Mehta, Ashray Gunjur, Prashant Gupta, Victoria Harle, Kaori Koga, I. Matzusaki, Masakazu Fujimoto, Katharina Wiedemeyer, A. Stratigos, Anca Oniscu, Kun Wang, Eytan Ruppin, Pieter Demetter, Ian M. Frayling, Mark J. Arends, Thomas Brenn, David J. Adams · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-66584-0 · 被引用次数：2 · 研究领域：Nonmelanoma Skin Cancer Studies、Cancer and Skin Lesions、Genetic and rare skin diseases.

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.