The purpose of this pilot study was to evaluate the utility of NanoString probe technology for the detection of MYB-NFIB transcripts in archival ACC tissue.
Recent studies have indicated that a recurrent t(6;9)(q22-23;p23-24) chromosomal translocation in salivary adenoid cystic carcinoma (ACC) results in a MYB proto-oncogene transcription factor-nuclear factor I/B <i>(MYB-NFIB)</i> gene fusion, which has not previously been detected in any non-ACC carcinomas of the head and neck.
The aim of this meta-analysis is to evaluate myeloblastosis (MYB) as a prognostic marker for patients with adenoid cystic carcinoma (ACC) with respect to MYB gene fusion, MYB protein expression, and tumor sites.
Retinoic acid agonists inhibited tumor growth in vivo in ACC patient-derived xenograft models and decreased MYB binding at translocated enhancers, thereby potentially diminishing the MYB positive feedback loop driving ACC.
Expression of <i>MYB</i> or <i>MYBL1</i> was closely correlated to the expression of the <i>SOX4</i> and <i>EN1</i> genes, suggesting that they are direct targets of Myb proteins in ACC tumors.
Although MYB-NFIB oncogene fusion and Notch1 mutation have been identified in ACC, little is known about the expression and clinical significance of Notch1 and its target gene fatty acid binding protein 7 (FABP7) in tracheobronchial ACC.
Strong, diffuse nuclear labeling for MYB is more sensitive than MYB fluorescence in situ hybridization for breast ACC and can be used to support a diagnosis of ACC in a cribriform or basaloid lesion in the breast.
<i>MYB</i> gene translocation was observed and significantly correlated with overexpression of MYB but did not correlate with FGFR1 phosphorylation or clinical response to dovitinib.<b>Conclusions:</b> Dovitinib produced few objective responses in patients with ACC but did suppress the TGR with a PFS that compares favorably with those reported with other targeted agents.
Elevated MYB expression has been documented in adenoid cystic carcinoma (ACC), cylindroma, and spiradenoma, but the specificity of this finding is unknown.
The high prevalence of alterations leading to high expression of the MYB transcription factor family suggests that targeted approaches developed to suppress the expression of these oncogenic transcription factors and/or the transcriptional activity of these proteins would be a rational therapeutic approach to investigate in ACC.
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.
This phase II trial of the tyrosine kinase inhibitor (TKI) axitinib (Pfizer) tested the hypothesis that targeting pathways activated by MYB can be therapeutically effective for ACC.
Thus, our study identifies super-enhancer translocations that drive MYB expression and provides insight into downstream MYB functions in alternate ACC lineages.
Interestingly, tumors with MYB and MYBL1 translocations displayed similar gene expression profiles, and the combined MYB and MYBL1 expression correlated with outcome, suggesting that the related MYB proteins are interchangeable oncogenic drivers in ACC.