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.
- MeSH
- adenoidně cystický karcinom genetika patologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA analýza MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory oka genetika patologie MeSH
- nádory slinných žláz genetika patologie MeSH
- nemoci slzného ústrojí genetika patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- triple-negativní karcinom prsu genetika patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- dítě MeSH
- dlouhodobá péče MeSH
- kojenec MeSH
- lidé MeSH
- nádory oka diagnóza genetika terapie MeSH
- předškolní dítě MeSH
- prenatální diagnóza MeSH
- retinoblastom diagnóza epidemiologie terapie MeSH
- rhabdomyosarkom diagnóza epidemiologie terapie MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- předškolní dítě MeSH
- MeSH
- chromozomální aberace MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- melanom epidemiologie genetika MeSH
- močovina MeSH
- nádory oka epidemiologie genetika MeSH
- senioři MeSH
- sexuální faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Geografické názvy
- Československo MeSH
