MYB, MYBL1, MYBL2, and NFIB Gene Alterations and MYC Overexpression in Salivary Gland Adenoid Cystic Carcinoma

Abstract

Aims

Adenoid cystic carcinoma (AdCC) is one of the most common salivary gland malignancies and the long-term prognosis is poor. In this study, we examined alterations of AdCC-associated genes, MYB, MYBL1, MYBL2, and NFIB, and their target molecules including MYC. The results were correlated to clinicopathological profile of the patients.

Methods And Results

Using paraffin tumor sections from 33 cases of salivary gland AdCC, we performed a detailed fluorescence in situ hybridization (FISH) analysis for gene splits and fusions of MYB, MYBL1, MYBL2, and NFIB. We found that 29/33 (88%) AdCC cases showed gene splits in either MYB, MYBL1, or NFIB. None of the cases showed an MYBL2 gene alteration. AdCCs were genetically divided into six gene groups, MYB-NFIB (n=16), MYB-X (n=4), MYBL1-NFIB (n=2), MYBL1-X (n=1), NFIB-X (n=6), and gene-split-negative (n=4). AdCC patients showing the MYB or MYBL1 gene splits were associated with microscopically positive surgical margins (p=0.0148) and overexpression of MYC (p=0.0164). MYC expression was detected in both ductal and myoepithelial tumor cells, and MYC overexpression was associated with shorter disease-free survival of the patients (p=0.0268).

Conclusions

The present study suggests that 1) nearly 90% of AdCCs may have gene alterations of either MYB, MYBL1, or NFIB, suggesting diagnostic utility of the FISH assay, 2) MYB or MYBL1 gene splits may be associated with local aggressiveness of the tumors and overexpression of MYC, which is one of the oncogenic MYB/MYBL1 targets, and 3) MYC overexpression may be a risk factor for disease-free survival in AdCC.

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