Alternative MYB Promoter Activity Is a Potential Prognostic Biomarker in Head and Neck Adenoid Cystic Carcinoma.

Abstract

Adenoid cystic carcinoma (ACC) is an aggressive therapy-resistant head and neck cancer with a high frequency of local recurrences and distant metastases. Activation of the MYB gene, encoding an oncogenic master transcription factor, is the key genomic hallmark of ACC and a potential therapeutic target. Here, we have investigated the clinical significance of alternative MYB promoter (MYB TSS2) activation in primary ACCs. MYB TSS2 activity was studied in 28 ACCs using MYB exon-specific qPCR assays. Overall survival (OS) and risk analyses were done to estimate the outcomes of MYB TSS2 high and low cases, respectively. The genomic and transcriptomic profiles of the ACCs were also analyzed in relation to MYB TSS2 activity. OS was significantly shorter among patients in the MYB TSS2 high group compared to the MYB TSS2 low group (p = 0.02). Multivariate analysis indicated that MYB TSS2 activity was a significant prognostic biomarker for OS (p = 0.03) that was independent of tumor grade and NOTCH1 mutation status. There was markedly higher MYB TSS2 activity in ACCs with 6q deletions compared to those without deletions (p = 0.04). Moreover, MYB TSS2 high tumors had an increased expression of cell cycle genes and known MYB target genes. The study demonstrates that alternative MYB promoter activity is a new potential prognostic biomarker for ACC and further strengthens the relevance of MYB-targeted therapy. Our findings indicate that MYB TSS2 high primary tumors are more aggressive and have a worse prognosis than MYB TSS2 low tumors.