Abstract

Adenoid cystic carcinoma (ACC), the second most common salivary gland malignancy, is notorious for poor prognosis, which reflects the propensity of ACC to progress to clinically advanced metastatic disease. Due to high long-term mortality and lack of effective systemic treatment, the slow-growing but aggressive ACC poses a particular challenge in head and neck oncology. Despite the advancements in cancer genomics, up until recently relatively few genetic alterations critical to the ACC development have been recognized. Although the specific chromosomal translocations resulting in MYB-NFIB fusions provide insight into the ACC pathogenesis and represent attractive diagnostic and therapeutic targets, their clinical significance is unclear, and a substantial subset of ACCs do not harbor the MYB-NFIB translocation. Strategies based on detection of newly described genetic events (such as MYB activating super-enhancer translocations and alterations affecting another member of MYB transcription factor family-MYBL1) offer new hope for improved risk assessment, therapeutic intervention and tumor surveillance. However, the impact of these approaches is still limited by an incomplete understanding of the ACC biology, and the manner by which these alterations initiate and drive ACC remains to be delineated. This manuscript summarizes the current status of gene fusions and other driver genetic alterations in ACC pathogenesis and discusses new therapeutic strategies stemming from the current research.

Highlights

  • Recurrent chromosomal translocations and resultant gene fusions have long been recognized as critical events in the oncogenesis of hematological malignancies and soft-tissue neoplasms

  • The identification of a fusion between MYBL1 and NFIB genes in tumors without MYB aberration [6, 7], demonstrates that the pathogenesis of adenoid cystic carcinoma (ACC) may be driven by genetic alterations in another member of the same transcription factor (TF) gene family

  • We summarize the current status of the genomic translocations in ACC, discuss challenges associated with underpinning their role in ACC pathogenesis and focus on possible clinical implications stemming from the current research

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Summary

Introduction

Recurrent chromosomal translocations and resultant gene fusions have long been recognized as critical events in the oncogenesis of hematological malignancies and soft-tissue neoplasms. The discovery of the translocation between chromosome 6q and 9p and the identification www.impactjournals.com/oncotarget of the resultant MYB-NFIB fusion in 2009, led to an important insight into the molecular pathogenesis of this malignancy and highlighted the tumor driving role of the MYB (myeloblastosis) proto-oncogene [4].

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