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, Frederic J. Kaye

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)12528-12542
Number of pages15
JournalOncotarget
Volume5
Issue number24
DOIs
StatePublished - 2014

Keywords

  • Adenoid cystic cancer
  • Extracellular matrix
  • MYB salivary gland cancer

ASJC Scopus subject areas

  • Oncology

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