ArticleJCI insight2021
The CRTC1-MAML2 fusion is the major oncogenic driver in mucoepidermoid carcinoma.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 66 citations in OpenAlex.
- SMARCA4-deficient lung adenocarcinoma with oral cavity metastasis: a case report.BMC oral health · 2026Article
- Contemporary Management of Malignancies of the Parotid Gland: A State-of-the-Art Review.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2026Review
- Bronchial mucoacinar carcinoma: a newly proposed subtype of mucoepidermoid carcinoma in the bronchus.Journal of clinical pathology · 2026Article
- A clinicopathologic and survival analysis of mucoepidermoid carcinoma of the breast.Contemporary oncology (Poznan, Poland) · 2026Article
- Case Report: Treatment of an unresectable mucoepidermoid carcinoma with osimertinib.Frontiers in oncology · 2026Article
- Challenges in the detection and assembly of virus integration structures in human genomes.Frontiers in oncology · 2026Review
- A case of infarcted Warthin tumor misdiagnosed as Warthin-like mucoepidermoid carcinoma: diagnosis confirmed byFrontiers in oncology · 2026Article
- Operculectomy Preceding a Mucoepidermoid Carcinoma Development: Case Report.Case reports in dentistry · 2026Article
- Methylation-based signature to distinguish indolent and aggressive prostate cancer.Biology open · 2025Article
- Durable Response to Lenvatinib in Platinum-Refractory Metastatic High-Grade Thymic Mucoepidermoid Carcinoma: A Case Report.JTO clinical and research reports · 2025Article
- Clinical Utility of Whole-Genome Sequencing to Aid Histologic Diagnosis and to Direct Personalized Medicine in Salivary Gland Cancer.JCO precision oncology · 2025Article
- NovelCancers · 2025Article
- Clinicopathologic Features, Management, and Outcomes Of Pediatric CRTC1::TRIM11 and MED15::ATF1 Tumors With Spitzoid Morphology: A Case Series.Pediatric blood & cancer · 2025Article
- Article
- Real-World Data Analysis of Genomic Alterations Detected by a Dual DNA-RNA Comprehensive Genomic Profiling Test.Cancer science · 2025Article
- Significance of Notch Signaling in Salivary Gland Development and Diseases.Journal of clinical medicine · 2025Review
- Cell culture in salivary gland tumor research: molecular insights of pathogenic targets and personalized medicine.Cytotechnology · 2025Review
- Comprehensive mutational profiling identifies new driver events in cutaneous leiomyosarcoma.The British journal of dermatology · 2025Article
- The Molecular Biology of MEC Salivary Gland Tumors.Annals of otolaryngology and rhinology · 2025Article
- Metastatic Thymic Mucoepidermoid Carcinoma: The Diagnostic Challenges and Role of CRTC1/MAML2 Translocation in Accurate Diagnosis and Treatment.Thoracic cancer · 2025Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
No effective systemic treatment is available for patients with unresectable, recurrent, or metastatic mucoepidermoid carcinoma (MEC), the most common salivary gland malignancy. MEC is frequently associated with a t(11;19)(q14-21;p12-13) translocation that creates a CRTC1-MAML2 fusion gene. The CRTC1-MAML2 fusion exhibited transforming activity in vitro; however, whether it serves as an oncogenic driver for MEC establishment and maintenance in vivo remains unknown. Here, we show that doxycycline-induced CRTC1-MAML2 knockdown blocked the growth of established MEC xenografts, validating CRTC1-MAML2 as a therapeutic target. We further generated a conditional transgenic mouse model and observed that Cre-induced CRTC1-MAML2 expression caused 100% penetrant formation of salivary gland tumors resembling histological and molecular characteristics of human MEC. Molecular analysis of MEC tumors revealed altered p16-CDK4/6-RB pathway activity as a potential cooperating event in promoting CRTC1-MAML2-induced tumorigenesis. Cotargeting of aberrant p16-CDK4/6-RB signaling and CRTC1-MAML2 fusion-activated AREG/EGFR signaling with the respective CDK4/6 inhibitor Palbociclib and EGFR inhibitor Erlotinib produced enhanced antitumor responses in vitro and in vivo. Collectively, this study provides direct evidence for CRTC1-MAML2 as a key driver for MEC development and maintenance and identifies a potentially novel combination therapy with FDA-approved EGFR and CDK4/6 inhibitors as a potential viable strategy for patients with MEC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.