CRTC1–MAML2 fusion in mucoepidermoid carcinoma of the breast

Abstract

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 CRTC1–MAML2 translocations. Exceedingly rare MEC of the breast demonstrate a basal‐like and often triple (oestrogen and progesterone receptor, HER2)‐negative immunophenotype, with a single case previously reported to show MAML2 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 CRTC1–MAML2 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 CRTC1–MAML2 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 SETD2 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.

Pleomorphic adenomas and mucoepidermoid carcinomas of the breast are underpinned by fusion genes

“…The HMGA2 and PLAG1 rearrangements, and the CRTC1-MAML2 fusion genes identified in the breast PAs and breast MECs of this study, have been reported in PAs and MECs arising in the salivary gland and in other anatomic locations [6][7][8]20,21,23,24 . Moreover, our findings on breast MECs are in agreement with the study by Bean et al 30 , who reported on the presence of the CRTC1-MAML2 fusion gene in two breast MECs.…”

“…1g and 3a), the hallmark genetic alteration of MECs arising in other anatomic origins [6][7][8] . These findings are in agreement with the study by Bean et al 30 , who reported on two breast MECs harboring the CRTC1-MAML2 fusion gene. The fusion gene identified in BMEC2 was predicted to result in a chimeric transcript encompassing exon 1 of CRTC1 and exons 2-5 of MAML2 (Fig.…”

“…MECs of the salivary glands and two breast MECs previously reported are characterized by the t(11:19) (q21;p13) translocation, which results in the CRTC1-MAML2 fusion gene 6,30 . CRTC1 encodes for the CREB-regulated transcriptional coactivator 1 (ref.…”

Molecular characterisation of metanephric adenomas beyond BRAF: genetic evidence for potential malignant evolution

“…Matched normal and tumour tissues were selected from five cases (MA1–MA4 and MA12), and only tumour tissue was selected from seven cases (MA5–MA11). Capture‐based next‐generation DNA sequencing was performed with an assay (UCSF500) that targets the coding regions of 479 cancer‐related genes, selected introns from 41 genes, and the TERT promoter (Table ), as previously described 17 …”

Conjunctival Adenosquamous Carcinoma Lacks MAML2 Translocation: A Variant of Squamous Cell Carcinoma With Mucoepidermoid Differentiation and Aggressive Behavior?

“…1 Consisting of squamous cells, mucous cells, and intermediate cells in variable proportions, another unifying feature of MEC is the chromosomal translocation fusing the MAML2 gene with the CRTC1 gene, or, less frequently, CRTC3 gene. 2-7…”