Development and characterization of xenograft model systems for adenoid cystic carcinoma2011-10-02 16:03:09
Laboratory Investigations; 2011 Oct; 91(10):1480-90
Christopher A Moskaluk, Alexander S Baras, Stefani A Mancuso, Hao Fan, Robert J Davidson, Dawn C Dirks, Wendy L Golden, and Henry F Frierson Jr
Adenoid cystic carcinoma (ACC) is one of the most common malignancies that arise in the salivary glands, with an incidence of 4.5 per 1,000,000. It can also develop in glandular tissue closely related to salivary glands such as the lacrimal gland, sinonasal passages, and tracheobronchial tree, as well as in glands of the breast, skin, and vulva. At all of these sites, it is characterized by a distinctive histology of basaloid epithelial cells arranged in cribriform, tubular, or solid patterns, usually demonstrating abundant hyaline extracellular matrix secretion and some degree of myoepithelial differentiation. ACC is generally a slow-growing tumor characterized by a protracted clinical course, usually well over 5 years in duration, marked by regional recurrence, distant metastasis, and/or spread along peripheral nerves of the head and neck. A recurrent chromosomal translocation, t(6;9)(q23;p21), has been identified in ACCs, and recently it has been discovered that in a majority of these tumors the MYB gene on chromosome 6 is fused to the 3′ terminus of the NFIB gene on chromosome 9, creating a fusion gene product resulting in increased MYB-related transcriptional activation.
It has been determined that stable cell lines with putative attribution of ACC derivation are either contaminants of other cell lines or do not have the characteristic MYB–NFIB translocation. Also, there are no animal models of this histologically and genetically defined tumor type. To address the paucity of experimental and preclinical model systems of ACC, we have been establishing xenograft tumors from clinical samples of ACC, with the hypothesis that such tumors will recapitulate morphologic, genetic, and gene expression signals of the human disease. We describe herein our experience with these models and their characterization.
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