Gene Mutations Linked to Salivary Gland Tumors

Research conducted at the Florida campus of The Scripps Research Institute (TSRI) has discovered links between a set of genes known to promote tumor growth and mucoepidermoid carcinoma, an oral cancer that affects the salivary glands. The discovery could help physicians develop new treatments that target the cancer’s underlying genetic causes. Baseball Hall of Famer Tony Gwynn (image) recently died from complication of salivary gland cancer at the age of 54, bringing this disease into national prominence and, in his case, was widely attributed to the lengthy use of chewing tobacco. The new research, recently published online ahead of print on July 28, 2014 by PNAS, shows that a pair of proteins joined together by a genetic mutation—known as CRTC1/MAML2 (C1/M2)—work with MYC, a protein commonly associated with other cancers, to promote the oral cancer’s growth and spread. “This research provides new insights into the molecular mechanisms of these malignancies and points to a new direction for potential therapies,” says TSRI biologist Michael Conkright, Ph.D., who led the study. The C1/M2 protein is created when the genes encoding CRTC1 and MAML2 mutate into a single gene through a process known as chromosomal translocation. Such mutant “chimera” genes are linked to the formation of several forms of cancer. The team discovered that the C1/M2 protein further activates genetic pathways regulated by MYC, in addition to CREB, to begin a series of cellular changes leading to the development of mucoepidermoid carcinoma. “The identification of unique interactions between C1/M2 and MYC suggests that drugs capable of disrupting these interactions may have therapeutic potential in the treatment of mucoepidermoid carcinomas, ” said Antonio L.
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