Comprehensive analysis of the MYB-NFIB gene fusion in salivary adenoid cystic carcinoma: Incidence, variability, and clinicopathologic significance.
OBJECTIVE
The objectives of this study were to determine the incidence of the MYB-NFIB fusion in salivary adenoid cystic carcinoma (ACC), to establish the clinicopathologic significance of the fusion, and to analyze the expression of MYB in ACCs in the context of the MYB-NFIB fusion.


METHODS
We did an extensive analysis involving 123 cancers of the salivary gland, including primary and metastatic ACCs, and non-ACC salivary carcinomas. MYB-NFIB fusions were identified by reverse transcriptase-PCR (RT-PCR) and sequencing of the RT-PCR products, and confirmed by fluorescence in situ hybridization. MYB RNA expression was determined by quantitative RT-PCR and protein expression was analyzed by immunohistochemistry.


RESULTS
The MYB-NFIB fusion was detected in 28% primary and 35% metastatic ACCs, but not in any of the non-ACC salivary carcinomas analyzed. Different exons in both the MYB and NFIB genes were involved in the fusions, resulting in expression of multiple chimeric variants. Notably, MYB was overexpressed in the vast majority of the ACCs, although MYB expression was significantly higher in tumors carrying the MYB-NFIB fusion. The presence of the MYB-NFIB fusion was significantly associated (P = 0.03) with patients older than 50 years of age. No correlation with other clinicopathologic markers, factors, and survival was found.


CONCLUSIONS
We conclude that the MYB-NFIB fusion characterizes a subset of ACCs and contributes to MYB overexpression. Additional mechanisms may be involved in MYB overexpression in ACCs lacking the MYB-NFIB fusion. These findings suggest that MYB may be a specific novel target for tumor intervention in patients with ACC.
Mitani
Yoshitsugu
Y
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, 77030-4009, USA.
Li
Jie
J
Rao
Pulivarthi H
PH
Zhao
Yi-Jue
YJ
Bell
Diana
D
Lippman
Scott M
SM
Weber
Randal S
RS
Caulin
Carlos
C
El-Naggar
Adel K
AK
D003528:Carcinoma, Adenoid Cystic / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D014644:Genetic Variation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015994:Incidence; D008297:Male; D008875:Middle Aged; D051839:NFI Transcription Factors / Q000235:genetics*; D050596:Oncogene Fusion / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
D051839:NFI Transcription Factors; C110754:NFIB protein, human; D015514:Oncogene Proteins, Fusion; D020598:Proto-Oncogene Proteins c-myb