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

Yoshitsugu Mitani, Bin Liu, Pulivarthi H. Rao, Vishnupriya J. Borra, Mark Zafereo, Randal S. Weber, Merrill Kies, Guillermina Lozano, P. Andrew Futreal, Carlos Caulin, Adel K. El-Naggar

Research output: Contribution to journalArticlepeer-review

157 Scopus citations


Purpose: Adenoid cystic carcinoma (ACC) is an indolent salivary gland malignancy, characterized by t(6;9) translocations andMYB-NFIB gene fusions in approximately50%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, 50-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 50-NFIB gene fusions.

Original languageEnglish (US)
Pages (from-to)725-733
Number of pages9
JournalClinical Cancer Research
Issue number3
StatePublished - Feb 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine


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