Recurrent fusion of the v-myb avian myelobastosis viral oncogene homolog (MYB) and nuclear factor I/B (NFIB) generates the MYB-NFIB transcription factor, which has been detected in a high percentage of individuals with adenoid cystic carcinoma (ACC). To understand the functional role of this fusion protein in carcinogenesis, we generated a conditional mutant transgenic mouse that expresses MYB-NFIB along with p53 mutation in tissues that give rise to ACC: mammary tissue, salivary glands, or systemically in the whole body. Expression of the oncogene in mammary tissue resulted in hyperplastic glands that developed into adenocarcinoma in 27.3% of animals. Systemic expression of the MYB-NFIB fusion caused more rapid development of this breast phenotype, but mice died due to abnormal proliferation in the glomerular compartment of the kidney, which led to development of glomerulonephritis. These findings suggest the MYB-NFIB fusion is oncogenic and treatments targeting this transcription factor may lead to therapeutic responses in ACC patients.
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| http://dx.doi.org/10.18632/oncotarget.9426 | DOI Listing |
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Article Synopsis
- Adenoid cystic carcinomas (AdCC) of salivary gland origin are primarily defined by the presence of specific gene fusions, notably MYB::NFIB and MYBL1::NFIB, with sinonasal AdCC being particularly aggressive and lacking effective treatments.
- Researchers conducted an extensive analysis of 88 sinonasal AdCC cases using various techniques like NGS and FISH to identify gene fusions and mutations, finding that the majority harbored canonical fusions while some had noncanonical ones, with a few tumors showing no fusions at all.
- Mutational analysis revealed that about 68% of AdCCs tested (21 out of 31) had mutations in key oncogenes, highlighting potential areas for targeted
Targeted RNA Sequencing of Head and Neck Adenoid Cystic Carcinoma Reveals SEC16A::NOTCH1 Fusion and MET Exon 14 Skipping as Potentially Actionable Alterations.
Head Neck Pathol
November 2024
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
Purpose: Adenoid cystic carcinoma (AdCC) of the head and neck harbors MYB/MYBL1::NFIB fusions in around 60% of cases, with unfavorable long-term survival due to frequent recurrences and metastases, currently lacking effective targeted therapy. The study aims to identify actionable alterations and to elucidate the molecular underpinnings of MYB/MYBL1::NFIB-negative AdCC using a large targeted RNA sequencing panel.
Methods And Results: We retrospectively searched our MSK-Solid Fusion clinical sequencing database for head and neck AdCC sequenced between 2016 and 2023.
Adenoid Cystic Carcinoma with Sebaceous Differentiation and MYB::NFIB Fusion Arising in the External Auditory Canal.
Head Neck Pathol
September 2024
Department of Pathology, University of Chicago Medical Center, Chicago, IL, USA.
Article Synopsis
- Adenoid cystic carcinoma is a rare type of cancer that can happen in the outer ear canal.
- Sometimes, it can look like another type of skin cancer called sebaceous carcinoma, which makes it even rarer.
- In this case, doctors used images and tests to confirm the diagnosis, showing it had special features that were unusual for this kind of cancer.
Discovery of Novel TULP4/ACTN4/EWSR1/ACTB::MYB and ESRRG::DNM3 Fusions Expands Molecular Landscape of Adenoid Cystic Carcinoma Beyond Fusions Between MYB/MYBL1 and NFIB Genes.
Am J Surg Pathol
September 2024
Institute of Biomedicine, Pathology, University of Turku and Department of Pathology, Turku University Hospital, Turku, Finland.
Adenoid cystic carcinoma (AdCC) is one of the most common salivary gland malignancies and occurs in all major and minor salivary gland and seromucous gland sites. AdCCs of salivary gland origin have long been categorized as fusion-defined carcinomas owing to the almost consistent presence of fusion genes MYB::NFIB, or less commonly MYBL1::NFIB. We collected a cohort of 95 cases of AdCC, which were largely characterized by canonical fusions MYB::NFIB (49 cases) or MYBL1::NFIB (9 cases).
View Article and Find Full Text PDFMYB immunohistochemistry as a predictor of MYB::NFIB fusion in the diagnosis of adenoid cystic carcinoma of the head and neck.
Oral Surg Oral Med Oral Pathol Oral Radiol
December 2024
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands.
Objectives: Diagnosing adenoid cystic carcinoma (AdCC) is challenging due to histopathological variability and similarities with other tumors. In AdCC pathogenesis, the cellular myeloblastosis gene (c-MYB) often exhibits a MYB::NFIB fusion from a reciprocal translocation. This study aimed to assess the predictive accuracy of MYB immunohistochemistry for detecting this translocation compared to fluorescence in situ hybridization (FISH).
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