Adenoid cystic carcinoma (ACC)is among the most common malignancies to arise in salivary glands, but little is known of the molecular mechanisms responsible for this disease. Prior and preliminary studies have identified the long arm of chromosome 6 (6q) as an area frequently deleted in ACC. Common deletion events are markers of known tumor suppressor genes in other cancers and the goal of this project is to test the hypothesis that a novel tumor suppressor gene exists on 6q which is responsible for ACC tumorigenesis.
The Specific Aims are to 1) provide a more definitive genetic map of the common ACC deletion area on 6q in order to narrow the number of candidate genes that will have to be screened, 2) assay candidate genes for genetic characteristics of tumor suppressor genes and 3) assay candidate genes for functional characteristics of tumor suppressor genes. The cell line ACC3, derived from an adenoid cystic carcinoma, has been found to have a 6q deletion, and in support of these Aims, the deletion event in this cell line will be better characterized. Chromosomal transfer experiments will be performed to determine if ACC3 can serve as a model system to test for functional tumor suppression by genetic material on the 6q locus. Resources available to achieve these goals and carry out these Aims include an existing collection of primary ACC tumor samples, an established ACC tumor registry, a salivary gland tumor tissue microarray and oligonucleotide microarray gene expression data on a set of AGO and normal salivary gland tissue. ? ? There is no effective therapy for ACC, which is surgically non-resectable. Since there is an incomplete understanding of the molecular pathogenesis of ACC, there is little basis on which to rationally design and/or test new therapies. This application will address this deficiency. Since chromosome 6q deletions are common in other malignancies (breast cancer, ovarian cancer, melanoma) this knowledge may be generalizable to a larger population. Since AGO appears to have a smaller number of genetic changes than these other malignancies, it may serve as a simpler system to identify the 6q tumor suppressor gene.
| Moskaluk, Christopher A; Baras, Alexander S; Mancuso, Stefani A et al. (2011) Development and characterization of xenograft model systems for adenoid cystic carcinoma. Lab Invest 91:1480-90 |
| Pramoonjago, P; Baras, A S; Moskaluk, C A (2006) Knockdown of Sox4 expression by RNAi induces apoptosis in ACC3 cells. Oncogene 25:5626-39 |
| Rutherford, Sue; Hampton, Garret M; Frierson, Henry F et al. (2005) Mapping of candidate tumor suppressor genes on chromosome 12 in adenoid cystic carcinoma. Lab Invest 85:1076-85 |
