MYB-NFIB fusion transcript in adenoid cystic carcinoma: Current state of knowledge and future directions. (August 2022)

• Record Type: Journal Article
• Authors: Wagner, Vivian P.; Bingle, Colin D.; Bingle, Lynne
• Is Part Of: Critical reviews in oncology/hematology. Volume 176(2022)
• Publication Date: 2022-08
• Subjects: Head and neck neoplasms -- Salivary gland tumors -- Chromosomal translocation -- Fusion proteins -- Oncogenes; Oncology -- Periodicals; Hematology -- Periodicals; 616.994
• DOI: 10.1016/j.critrevonc.2022.103745
• Languages: English
• ISSNs: 1040-8428

Abstract

Abstract: Adenoid cystic carcinoma (ACC) is the most common type of salivary gland cancer that can also arise in other primary sites. Regardless of the site, most ACC cases carry a recurrent chromosomal translocation - t(6;9)(q22–23;p23–24) - involving the MYB oncogene and the NFIB transcription factor. Generally, a long sequence of MYB is fused to the terminal exons of NFIB, yet the break can occur in different exons for both genes, resulting in multiple chimeric variants. The fusion status can be determined by a number of methods, each of them with particular advantages. In vitro and in vivo studies have been conducted to understand the biological consequences of MYB-NFIB translocation, and such findings could contribute to improving the current inefficient therapeutic options for disseminated ACC. This review provides a discussion on relevant evidence in the context of ACC MYB-NFIB translocations to determine the current state of knowledge and discuss future directions. Graphical Abstract: ga1 Highlights: MYB-NFIB fusions in ACC generate multiple transcript variants due to different breakpoints in both genes. FISH is more reliable than PCR in determining ACC fusion status if primers used are not capable of detecting all breakpoints. Super-enhancers present in the rearranged portions of NFIB play a role in Myb overactivation. MYB-NFIB fusion triggers cell proliferation, survival and cell cycle progression, by activating several MYB-regulated genes. MYB-targeting therapies have demonstrated promising results in in vitro and in vivo experimental studies.