MYBL1 rearrangements and MYB amplification in breast adenoid cystic carcinomas lacking the MYB-NFIB fusion gene

Jisun Kim, Felipe C. Geyer, Luciano G. Martelotto, Charlotte Ky Ng, Raymond S. Lim, Pier Selenica, Anqi Li, Fresia Pareja, Nicola Fusco, Marcia Edelweiss, Rahul Kumar, Rodrigo Gularte-Merida, Andre N. Forbes, Ekta Khurana, Odette Mariani, Sunil Badve, Anne Vincent-Salomon, Larry Norton, Jorge S. Reis-Filho, Britta Weigelt

Research output: Contribution to journalArticlepeer-review


Breast adenoid cystic carcinoma (AdCC), a rare type of triple-negative breast cancer, has been shown to be driven by MYB pathway activation, most often underpinned by the MYB-NFIB fusion gene. Alternative genetic mechanisms, such as MYBL1 rearrangements, have been reported in MYB-NFIB-negative salivary gland AdCCs. Here we report on the molecular characterization by massively parallel sequencing of four breast AdCCs lacking the MYB-NFIB fusion gene. In two cases, we identified MYBL1 rearrangements (MYBL1-ACTN1 and MYBL1-NFIB), which were associated with MYBL1 overexpression. A third AdCC harboured a high-level MYB amplification, which resulted in MYB overexpression at the mRNA and protein levels. RNA-sequencing and whole-genome sequencing revealed no definite alternative driver in the fourth AdCC studied, despite high levels of MYB expression and the activation of pathways similar to those activated in MYB-NFIB-positive AdCCs. In this case, a deletion encompassing the last intron and part of exon 15 of MYB, including the binding site of ERG-1, a transcription factor that may downregulate MYB, and the exon 15 splice site, was detected. In conclusion, we demonstrate that MYBL1 rearrangements and MYB amplification probably constitute alternative genetic drivers of breast AdCCs, functioning through MYBL1 or MYB overexpression. These observations emphasize that breast AdCCs probably constitute a convergent phenotype, whereby activation of MYB and MYBL1 and their downstream targets can be driven by the MYB-NFIB fusion gene, MYBL1 rearrangements, MYB amplification, or other yet to be identified mechanisms.

Original languageEnglish
Pages (from-to)143-150
JournalJournal of Pathology
Issue number2
Publication statusPublished - 2018


  • Adenoid cystic carcinoma
  • Breast
  • MYB
  • MYB-NFIB fusion gene
  • MYBL1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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