Project description:Tumors of the major and minor salivary gland encompass a diverse spectrum of diagnostically challenging neoplasms. Recent studies have identified several gene fusions and somatic mutations that are specific or highly enriched in certain salivary gland tumor entities and can assist histopathological diagnosis. Still, there is an unmet need to identify additional diagnostic biomarkers for entities lacking specific alterations. In this study, we collected a comprehensive cohort of 363 cases encompassing 20 different salivary gland tumor entities and explored the potential of DNA methylation to classify these tumors. We were able to show that most entities show specific epigenetic signatures and present a machine learning algorithm that can be used to classify diagnostically challenging cases.
Project description:Rapamycin treatment of AKT induced salivary gland tumors Normal tissue (parotid and submandibular), untreated tumor tissue, and tumor tissue treated for 3/14 days
Project description:Copy-number and loss of heterozygosity analysis of salivary gland tumors in a proband with attenuated familial adenomatous polyposis (AFAP), using Affymetrix OncoScan and CytoScan HD arrays
Project description:Salivary gland adenoid cystic carcinoma (ACC) is a rare malignancy amongst head and neck tumors that is poorly understood on a molecular level. We sought to perform a comprehensive approach for novel oncogene candidate screening under the control of promoter methylation in order to learn more about the molecular basis of this unusual disease. We performed global demethylation of normal salivary gland cell strains using 5-aza-deoxycytidine (5-Aza dC) and trichostatin (TSA). Expression arrays were performed, and the profiles of treated and untreated cells compared. We then used expression microarray analysis of primary ACC and normal salivary gland samples to generate ACC-specific expression profiling. Next, we integrated the two profiles to identify a subset of genes for further validation of decreased methylation in the promoter region in ACC vs normals. Finally, only genes that showed decreased methylation in ACC compared to normal were further validated for mRNA, protein, and promoter methylation levels in a larger ACC cohort.
Project description:Salivary glands that produce and secret saliva, which is essential for lubrication, digestion, immunity, and oral homeostasis, consist of diverse cells. The long-term maintenance of diverse salivary gland cells in organoids remains problematic. Here, we established long-term murine salivary gland organoids from 3 major salivary glands, including parotid gland (PG), submandibular gland (SMG), and sublingual gland (SLG). Murine salivary gland organoids expressed gland-specific genes and proteins of acinar, myoepithelial, and duct cells. Organoids were maintained in growth media (named GEM) and further underwent differentiation in differentiation media (named DAM). Our study will provide an experimental platform for the exploration of mechanisms involvled in tissue regeneration, development, or several salivary gland diseases.
Project description:We established patient-derived organoids and monolayer culture cells from the salivary gland cancer cases. To compare the RNA profiles of primary culture cells (Organoids and monolayer culture cells) and their parental tumors, we isolated total RNA from 2 cases of the salivary gland cancer and performed transcriptome sequencing for the organoids, monolayer culture cells, and their parental tumors of both cases. Case 6 is a case of adenoid cystic carcinoma and Case 11 is a case of salivary duct carcinoma.
Project description:Salivary gland adenoid cystic carcinoma (ACC) is a rare malignancy amongst head and neck tumors that is poorly understood on a molecular level. We sought to perform a comprehensive approach for novel oncogene candidate screening under the control of promoter methylation in order to learn more about the molecular basis of this unusual disease.
Project description:Loss of Irf6 leads to disruption of branching morphogenesis and secretory acnii formation in salivary gland. To determine the differentially expressed genes in Irf6 mutant, embryonic salivary gland tissues were extracted at E14.5.