Oncotarget

Priority Research Papers:

A unifying gene signature for adenoid cystic cancer identifies parallel MYB-dependent and MYB-independent therapeutic targets

Ruli Gao, Chunxia Cao, Min Zhang, Maria-Cecilia Lopez, Yuanqing Yan, Zirong Chen, Yoshitsugu Mitani, Li Zhang, Maria Zajac-Kaye, Bin Liu, Lizi Wu, Rolf Renne, Henry V. Baker, Adel El-Naggar and Frederic J. Kaye _

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Oncotarget. 2014; 5:12528-12542. https://doi.org/10.18632/oncotarget.2985

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Abstract

Ruli Gao1,2, Chunxia Cao1, Min Zhang1, Maria-Cecilia Lopez3, Yuanqing Yan2, Zirong Chen3, Yoshitsugu Mitani4, Li Zhang5, Maria Zajac-Kaye6, Bin Liu7, Lizi Wu3, Rolf Renne3, Henry V. Baker3, Adel El-Naggar4 and Frederic J. Kaye1,2

1 Department of Medicine, Division of Hematology and Oncology, College of Medicine, University of Florida, Gainesville, FL, USA

2 Genetics & Genomics Graduate Program, Genetics Institute, College of Medicine, University of Florida, Gainesville, FL, USA

3 Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA

4 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

5 Department of Computational Biology and Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

6 Department of Anatomy & Cell Biology, College of Medicine, University of Florida, Gainesville, FL, USA

7 Department of Molecular Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence:

Frederic J. Kaye, email:

Keywords: MYB salivary gland cancer, adenoid cystic cancer, extracellular matrix

Received: October 02, 2014 Accepted: December 09, 2014 Published: December 10, 2014

Abstract

MYB activation is proposed to underlie development of adenoid cystic cancer (ACC), an aggressive salivary gland tumor with no effective systemic treatments. To discover druggable targets for ACC, we performed global mRNA/miRNA analyses of 12 ACC with matched normal tissues, and compared these data with 14 mucoepidermoid carcinomas (MEC) and 11 salivary adenocarcinomas (ADC). We detected a unique ACC gene signature of 1160 mRNAs and 22 miRNAs. MYB was the top-scoring gene (18-fold induction), however we observed the same signature in ACC without detectable MYB gene rearrangements. We also found 4 ACC tumors (1 among our 12 cases and 3 from public databases) with negligible MYB expression that retained the same ACC mRNA signature including over-expression of extracellular matrix (ECM) genes. Integration of this signature with somatic mutational analyses suggests that NOTCH1 and RUNX1 participate with MYB to activate ECM elements including the VCAN/HAPLN1 complex. 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. In summary, we identified a unique ACC signature with parallel MYB-dependent and independent biomarkers and identified VCAN/HAPLN1 complexes as a potential target.


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