Adenoid cystic carcinoma is among the most frequent malignancies in the salivary and lacrimal glands and has a grave prognosis characterized by frequent local recurrences, distant metastases, and tumor-related mortality. Conversely, adenoid cystic carcinoma of the breast is a rare type of triple-negative (estrogen and progesterone receptor, HER2) and basal-like carcinoma, which in contrast to other triple-negative and basal-like breast carcinomas has a very favorable prognosis. Irrespective of site, adenoid cystic carcinoma is characterized by gene fusions involving MYB, MYBL1, and NFIB, and the reason for the different clinical outcomes is unknown. In order to identify the molecular mechanisms underlying the discrepancy in clinical outcome, we characterized the phenotypic profiles, pattern of gene rearrangements, and global microRNA expression profiles of 64 salivary gland, 9 lacrimal gland, and 11 breast adenoid cystic carcinomas. All breast and lacrimal gland adenoid cystic carcinomas had triple-negative and basal-like phenotypes, while salivary gland tumors were indeterminate in 13% of cases. Aberrations in MYB and/or NFIB were found in the majority of cases in all three locations, whereas MYBL1 involvement was restricted to tumors in the salivary gland. Global microRNA expression profiling separated salivary and lacrimal gland adenoid cystic carcinoma from their respective normal glands but could not distinguish normal breast adenoid cystic carcinoma from normal breast tissue. Hierarchical clustering separated adenoid cystic carcinomas of salivary gland origin from those of the breast and placed lacrimal gland carcinomas in between these. Functional annotation of the microRNAs differentially expressed between salivary gland and breast adenoid cystic carcinoma showed these as regulating genes involved in metabolism, signal transduction, and genes involved in other cancers. In conclusion, microRNA dysregulation is the first class of molecules separating adenoid cystic carcinoma according to the site of origin. This highlights a novel venue for exploring the biology of adenoid cystic carcinoma.

Bioptic Laboratory Ltd Molecular Pathology Laboratory Pilsen Czech Republic

Department of Clinical Research Unit of Human Genetics University of Southern Denmark Odense Denmark

Department of Ophthalmology Rigshospitalet Glostrup Copenhagen Denmark

Department of Ophthalmology Zealand University Hospital Roskilde Denmark

Department of ORL Head and Neck Surgery Odense University Hospital Odense Denmark

Department of Otorhinolaryngology and Maxillofacial Surgery Zealand University Hospital Køge Denmark

Department of Otorhinolaryngology Head and Neck Surgery and Audiology Rigshospitalet Copenhagen Denmark

Department of Pathology Aalborg University Hospital Aalborg Denmark

Department of Pathology Aarhus University Hospital Aarhus Denmark

Department of Pathology Faculty of Medicine Charles University Prague Pilsen Czech Republic

Department of Pathology Herlev Hospital University of Copenhagen Herlev Denmark

Department of Pathology Odense University Hospital Odense Denmark

Department of Pathology Rigshospitalet Copenhagen Denmark

Department of Pathology Zealand University Hospital Roskilde Denmark

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