The molecular cartography of malignant and benign sebaceous tumours
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Nature Publishing Group UK
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Acknowledgements: The authors would like to thank M. Wicks and the Comparative Pathology Workbench97 (University of Edinburgh) and the collaborating institutions and their Biobanks (Pathology department, Western General Hospital, The University of Edinburgh, Edinburgh, United Kingdom; Dermatopathology laboratory – Department of Dermatology, Centre Hospitalier Universitaire Saint-Pierre – Université libre de Bruxelles, Belgium; Pathology department, Bordet Institute, Université libre de Bruxelles, Belgium; Department of Pathology, Faculty of Medicine, Fukuoka University Hospital, Fukuoka, Japan; Department of Diagnostic Pathology, Wakayama Medical University, Wakayama, Japan; Department of Pathology & Laboratory Medicine, The Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Canada; Pathology department, Andreas Sygros Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece), as well as Dr J. André (Dermatopathology laboratory – Department of Dermatology, Centre Hospitalier Universitaire Saint-Pierre – Université libre de Bruxelles, Belgium), Dr G. Beniuga (Pathology department of the Institut de Pathologie et Génétique, Gosselies, Belgium), Dr D. d’Olne (Centre du Diamant, Brussels, Belgium), Prof L. Marot (Pathology department of Cliniques universitaires Saint-Luc, Brussels, Belgium), Dr N. Renard (Pathology department of Centre Hospitalier de Wallonie picarde, Tournai, Belgium), Prof. W. Hartschuh (Dermatology department, University of Heidelberg, Germany), Dr B. Doukouré (Pathology department, University of Félix Houphouet-Boigny, Ivory Coast) and Prof. M.O.A. Samaila (Pathology department, Ahmadu Bello University & Ahmadu Bello University Teaching Hospital Zaria, Nigeria) for their collaboration. We also thank Dr D. Franck and Dr A. Léonard for the provided clinical pictures and the referring dermatologists/clinicians and the patients and their families. This project was supported by the Medical Research Council [MR/V000292/1– The Genomic Atlas of Dermatological Tumours (DERMATLAS)], the Wellcome Trust [220540/Z/20/A], and in part by the Intra-mural Research Programme of the National Institutes of Health, National Cancer Institute, the Pathological Society of Great Britain & Ireland, and the André Vésale Association. I.F. was supported by Wallonia-Brussels International (Belgium), the Horlait-Dapsens Foundation, the F.R.S.-FNRS - Télévie (grant 7.4521.20) and the Lambeau-Marteaux Funds. O.M.R was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014) and the Medical Research Council (UK; MC_UU_00002/16). OC was supported by a doctoral fellowship from the University of Cambridge Harding Distinguished Postgraduate Scholars Programme.
Publication status: Published
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.
Publication status: Published
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.