Adenoid cystic carcinoma

It is the third-most common malignant salivary gland tumor overall (after mucoepidermoid carcinoma and polymorphous adenocarcinoma). It represents 28% of malignant submandibular gland tumors, making it the single most common malignant salivary gland tumor in this region. Patients may survive for years with metastases because this tumor is generally well-differentiated and slow growing. In a 1999 study of a cohort of 160 ACC patients, disease-specific survival was 89% at 5 years, but only 40% at 15 years, reflecting deaths from late-occurring metastatic disease.

Cause

Activation of the oncogenic transcription factor gene MYB is the key genomic event of ACC and seen in the vast majority of cases. Most commonly, MYB is activated through gene fusion with the transcription factor encoding NFIB gene as a result of a t(6;9) translocation. Alternatively, MYB is activated by copy number gain or by juxtaposition of enhancer elements in the vicinity of the MYB gene. In a subset of ACCs, the closely related MYBL1 gene is fused to NFIB or to other fusion partners.

MYB drives proliferation of ACC cells and regulates genes involved in cell cycle control, DNA replication and repair, and RNA processing. Thus, the MYB oncogene is a potential diagnostic and therapeutic target in ACC.

ACC has a relatively quiet genome with few recurrent copy number alterations or point mutations, consistent with the view that MYB and MYBL1 are the main oncogenic drivers of the disease.