CRTC1–MAML2 fusion in mucoepidermoid carcinoma of the breast

Aims Mucoepidermoid carcinomas ( MEC ) are the most common malignant neoplasms of salivary glands, but are uncommon in other sites. Salivary gland MEC are most frequently associated with CRTC 1 – MAML 2 translocations. Exceedingly rare MEC of the breast demonstrate a basal‐like and often triple (oestrogen and progesterone receptor, HER 2)‐negative immunophenotype, with a single case previously reported to show MAML 2 rearrangement, although the fusion partner was not known. Comprehensive genomic studies of breast MEC are lacking. In this study, we analysed the immunophenotype and molecular landscape of two breast MEC to elucidate the pathogenesis of these rare tumours. Methods and results Two breast MEC were subjected to capture‐based next‐generation DNA sequencing of 479 cancer‐related genes. The presence of the CRTC 1– MAML 2 fusion transcript was interrogated by reverse transcriptase–polymerase chain reaction. In addition, the immunoprofiles of breast MEC were compared to salivary gland MEC . Both breast MEC harboured CRTC 1– MAML 2 fusions. In contrast to most triple‐negative breast carcinomas of no special type, the mutational burden of MEC was very low, with one case demonstrating only an inactivating SETD 2 mutation, and the other harbouring no somatic variants in genes on the panel. No copy number alterations were identified. The immunoprofiles of breast and salivary gland MEC were overlapping, but not identical. Conclusions The findings highlight MEC as a breast cancer subtype more closely related to its salivary gland counterpart than to basal‐like/triple‐negative breast cancers of no special type.