Novel MYBL1 Gene Rearrangements with Recurrent MYBL1-NFIB Fusions in Salivary Adenoid Cystic Carcinomas Lacking t(6;9) Translocations

Clin Cancer Res. 2016 Feb 1;22(3):725-33. doi: 10.1158/1078-0432.CCR-15-2867-T. Epub 2015 Dec 2.


Purpose: Adenoid cystic carcinoma (ACC) is an indolent salivary gland malignancy, characterized by t(6;9) translocations and MYB-NFIB gene fusions in approximately 50% of the tumors. The genetic alterations underlying t(6;9)-negative and t(6;9)-positive/MYB-NFIB fusion-negative ACC remain unknown. To uncover the genetic alterations in ACC lacking the canonical translocation and fusion transcript and identify new abnormalities in translocation positive tumors.

Experimental design: We performed whole-genome sequencing in 21 salivary ACCs and conducted targeted molecular analyses in a validation set (81 patients). Microarray gene-expression data were also analyzed to explore the biologic differences between fusion positive and negative tumors.

Results: 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. All MYBL1 alterations involved deletion of the C-terminal negative regulatory domain and were associated with high MYBL1 expression. Reciprocal MYB and MYBL1 expression was consistently found in ACCs. In addition, 5'-NFIB fusions that did not involve MYB/MYBL1 genes were identified in a subset of t(6;9)-positive/fusion-negative tumors. We also delineated distinct gene-expression profiles in ACCs associated with the length of the MYB or MYBL1 fusions, suggesting a biologic importance of the C-terminal part of these fusions.

Conclusions: Our study defines new molecular subclasses of ACC characterized by MYBL1 rearrangements and 5'-NFIB gene fusions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Adenoid Cystic / genetics*
  • Carcinoma, Adenoid Cystic / mortality
  • Carcinoma, Adenoid Cystic / pathology
  • Chromosome Breakpoints
  • Chromosomes, Human, Pair 8
  • Chromosomes, Human, Pair 9
  • Cluster Analysis
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Order
  • Genome, Human
  • Genomics / methods
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • NFI Transcription Factors / genetics*
  • Oncogene Proteins, Fusion / genetics*
  • Prognosis
  • Proto-Oncogene Proteins / genetics*
  • Reproducibility of Results
  • Salivary Gland Neoplasms / genetics*
  • Salivary Gland Neoplasms / mortality
  • Salivary Gland Neoplasms / pathology
  • Trans-Activators / genetics*
  • Translocation, Genetic*


  • MYBL1 protein, human
  • NFI Transcription Factors
  • NFIB protein, human
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • Trans-Activators