Abstract
PurposeAdenoid cystic carcinoma (ACC) is a rare neurotropic cancer with slow progression occurring in salivary glands and less frequently in other body parts. ACC is featured by hyperchromatic nuclei and various mutations in genes encoding chromatin-related machineries. The ACC treatment is mainly limited to the radical surgery and radiotherapy while the chemotherapy remains ineffective. As the knowledge about molecular basis of ACC development is limited, we investigated here the molecular features of this disease.Patients and methodsThis study included 50 patients with ACC. Transcript profiling of available ACC samples vs normal salivary gland tissue, quantitative real-time PCR (qRT-PCR) transcript level measurements and the immunohistochemistry (IHC) for SWI/SNF chromatin remodeling complex (CRC) subunits and androgen receptor on surgery-derived paraffin-embedded samples were performed.ResultsTranscriptomic study followed by Gene Ontology classification indicated alteration of chromatin-related processes, including downregulated transcript levels of main SWI/SNF CRC subunits and elevated expression of BRM ATPase-coding SMARCA2 gene in ACC. Subsequent IHC indicated broad accumulation of BRM ATPase and several SWI/SNF subunits, suggesting affected control of their protein level in ACC. The IHC revealed ectopic, heterogeneous expression of androgen receptor (AR) in some ACC cells.ConclusionsOur study indicated that ACC features aberrant expression of genes controlling chromatin status and structure. We found that the balance between SWI/SNF classes is moved towards the BRM ATPase-containing complex in ACC. As BRM is known to be involved in chemoresistance in cancer cells, this observation may be the likely explanation for ACC chemoresistance.
Highlights
Adenoid cystic carcinoma (ACC) is an uncommon malignancy
Our findings suggest an important role of SWI/SNF chromatin remodeling complex (CRC) impairment in the adenoid cystic carcinoma development and provided a likely explanation of the ACC resistance to various specific chemotherapy treatments
Given this fact we decided to investigate the transcriptional profiles of ACC samples and compare them with transcript profiles of normal tissue to identify the molecular features which could be helpful in the explanation of such severe chemoresistancy of ACC
Summary
Adenoid cystic carcinoma (ACC) is an uncommon malignancy. Other localizations include paranasal sinuses, larynx, lacrimal glands, bronchi, mammary and skin (Coca-Pelaz et al 2015; Dillon et al 2016). This type of cancer most frequently occurs between the fourth and the sixth decades of life. ACC is rather indolent disease with slow growth and late development of distant metastases, but it may be fast-growing malignancy with early distant spread. When diagnosed at an early stage, it usually appears as a single and oval lesion (usually with smaller than 6 cm diameter) well defined and
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