Transcriptional Mechanisms by the Coregulator MAML1
CURRENT PROTEIN & PEPTIDE SCIENCE
Authors: Ribeiro, M. Saint Just; Wallberg, A. E.
Abstract
The Mastermind-like (MAML) proteins are transcriptional coactivators for Notch signaling, an evolutionarily conserved pathway that plays several key roles in development and in human disease. The MAML family contains MAML1, MAML2, and MAML3. More recently, MAML1 has been shown to function as a coactivator for the tumor suppressor p53, the MADS box transcription enhancer factor (MEF) 2C, and beta-catenin. In addition, MAML1 has been reported to interact with the histone acetyltransferase p300, and this interaction increases p300 activity. Furthermore, MAML1 binds to CDK8, which is a subunit of the Mediator complex. The function of MAML1 as a coactivator for diverse activators, and MAML1 interaction with broadly used coactivators, suggests that MAML1 might be a key molecule that connects various signaling pathways to regulate cellular processes in normal cells and in human disease.
Mucoepidermoid Carcinoma of the Lacrimal Sac: Clinical-Pathologic Analysis, Including Molecular Genetics
OCULAR ONCOLOGY AND PATHOLOGY
Authors: Gervasio, Kalla A.; Zhang, Paul J. L.; Penne, Robert B.; Stefanyszyn, Mary A.; Eagle, Ralph C., Jr.; Puthiyaveettil, Raghunath; Milman, Tatyana
Abstract
Purpose: The aim of this study was to assess whether mucoepidermoid carcinoma of the lacrimal sac is a counterpart of CRTC1/3-MAML2 gene fusion-related salivary gland mucoepidermoid carcinoma. Methods: In this retrospective observational case series, pathology records were searched for all cases of lacrimal sac mucoepidermoid carcinoma diagnosed between 1990 and 2018. Data collected included demographics, clinical findings, management, and follow-up. Pathologic parameters assessed included tumor morphology, immunohistochemistry, and MAML2 and EGFR fluorescence in situ hybridization (FISH) studies. Results: Six patients with mucoepidermoid carcinoma of the lacrimal sac, 5 males and 1 female, with a median age of 63 years (range 24-66) were identified. Five tumors were managed with radical resection and 1 patient underwent orbital exenteration. None of the patients developed recurrence or metastases with an average follow-up of 18 months (range 13-23). All tumors had morphologic and immunohistochemical features of mucoepidermoid carcinoma and overexpressed EGFR. MAML2 FISH was negative for MAML2 rearrangement in all tumors. EGFR FISH demonstrated EGFR amplification in 1 tumor. Conclusions: Mucoepidermoid carcinoma of the lacrimal sac is not a lacrimal sac counterpart of CRTC1/3-MAML2 gene fusion-related salivary gland mucoepidermoid carcinoma. EGFR pathway activation and EGFR amplification in a subset of these neoplasms suggest the potential role for anti-EGFR agents.
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