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.
The incidence of recurrent t(6;9) translocation of the MYB proto‑oncogene to NFIB (the gene that encodes nuclear factor 1 B‑type) in adenoid cystic carcinoma (ACC) tumour tissues is high.
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.
Finally, genomic analyses identified a novel <i>NFIB</i>-<i>MTFR2</i> fusion in an ACC tumor and confirmed previously reported fusions (<i>NTRK3</i>-<i>ETV6</i> and <i>MYB</i>-<i>NFIB)</i><b>Conclusions:</b> Sequential MEC PDX models preserved key patient features and enabled the identification of genetic events putatively contributing to increases in both CSC proportion and intrinsic tumorigenicity, which mirrored the patient's clinical course.<i></i>.
Breast adenoid cystic carcinoma (ACC) is a primary breast carcinoma that, like salivary gland ACC, displays the t(6;9) translocation resulting in the MYB-NFIB gene fusion and immunopositivity for MYB by immunohistochemistry (IHC).
Our findings suggest a separate role for NFIB in ACC oncogenesis and highlight important signaling pathways for future functional characterization and potential therapeutic targeting.
In addition to detecting the most common ACC translocation, t(6;9) fusing the MYB proto-oncogene to NFIB, we also detected previously unknown t(8;9) and t(8;14) translocations fusing the MYBL1 gene to the NFIB and RAD51B genes, respectively.
We identified a novel MYBL1-NFIB gene fusion as a result of t(8;9) translocation and multiple rearrangements in the MYBL1 gene in 35% of the t(6;9)-negative ACCs.
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.
Six of the 11 cutaneous and periorbital ACCs tested with reverse transcriptase polymerase chain reaction and/or fluorescence in situ hybridization had MYB rearrangements including 2 cases that expressed MYB-NFIB fusion transcripts.
A significant portion of adenoid cystic carcinoma (ACC) cases are characterized by a t(6;9)(q22-23;p23-24) translocation that originates a MYB-NFIB fusion oncogene.
We observed that forced MYB-NFIB expression in human salivary gland cells alters cell morphology and cell adhesion in vitro and depletion of VCAN blocked tumor cell growth of a short-term ACC tumor culture.
Recently, a specific translocation t(6;9) involving the v-myb avian myeloblastosis viral oncogene homolog (MYB) and nuclear factor I/B (NFIB) genes was identified in ACCs, in which it contributes to MYB overexpression.