t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway

Giovanni Tonon, Sanjay Modi, Lizi Wu, Akihito Kubo, Amy B. Coxon, Takefumi Komiya, Kevin O'Neil, Kristen Stover, Adel El-Naggar, James D. Griffin, Ilan R. Kirsch, Frederic J. Kaye

Research output: Contribution to journalArticlepeer-review

Abstract

Truncation of Notch1 has been shown to cause a subtype of acute leukemia1, and activation of Notch4 has been associated with mammary and salivary gland carcinomas of mice2. Here we identify a new mechanism for disrupting Notch signaling in human tumorigenesis, characterized by altered function of a new ortholog of the Drosophila melanogaster Notch co-activator molecule Mastermind. We cloned the t(11;19) translocation that underlies the most common type of human malignant salivary gland tumor. This rearrangement fuses exon 1 from a novel gene of unknown function at 19p13, termed mucoepidermoid carcinoma translocated 1 (MECT1), with exons 2-5 of a novel member of the Mastermind-like gene family (MAML2) at 11q21 (ref. 3). Similar to D. melanogaster Mastermind and MAML1 (refs. 4,5), full-length MAML2 functioned as a CSL (CBF-1, suppressor of hairless and Lag-1)-dependent transcriptional co-activator for ligand-stimulated Notch. In contrast, MECT1-MAML2 activated transcription of the Notch target gene HES1 independently of both Notch ligand and CSL binding sites. MECT1-MAML2 induced foci formation in RK3E epithelial cells, confirming a biological effect for the fusion product. These data suggest a new mechanism to disrupt the function of a Notch co-activator in a common type of malignant salivary gland tumor.

Original languageEnglish
Pages (from-to)208-213
Number of pages6
JournalNature Genetics
Volume33
Issue number2
DOIs
Publication statusPublished - Feb 1 2003

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Fingerprint Dive into the research topics of 't(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway'. Together they form a unique fingerprint.

Cite this