La cartografía molecular de tumores sebáceos malignos y benignos

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.