Rearrangements, Expression, and Clinical Significance of MYB and MYBL1 in Adenoid Cystic Carcinoma: A Multi-Institutional Study

Marta Persson, Mattias K. Andersson, Yoshitsugu Mitani, Margaret S. Brandwein-Weber, Henry F. Frierson, Christopher Moskaluk, Isabel Fonseca, Renata Ferrarotto, Werner Boecker, Thomas Loening, Adel K. El-Naggar, Göran Stenman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Adenoid cystic carcinoma (ṆACC) is an aggressive head and neck malignancy characterized by a t (6;9) translocation resulting in an MYB–NFIB gene fusion or, more rarely, an MYBL1 fusion. The true frequency and clinical significance of these alterations are still unclear. Here, we have used tissue microarrays and analyzed 391 ACCs and 647 non-ACC salivary neoplasms to study the prevalence, expression, and clinical significance of MYB/MYBL1 alterations by FISH and immunohistochemistry. Alterations of MYB or MYBL1 were found in 78% of the cases, of which 62% had MYB alterations and 16% had MYBL1 rearrangements. Overexpression of MYB/MYBL1 oncoproteins was detected in 93% of the cases. MYB split signal, seen in 39% of the cases, was specific for ACC and not encountered in non-ACC salivary tumors. Loss of the 3′-part of MYB was enriched in grade 3 tumors and was a significant independent prognostic biomarker for overall survival in multivariate analyses. We hypothesize that loss of the 3′-part of MYB results from an unbalanced t(6;9) leading to an MYB–NFIB fusion with concomitant loss of the segment distal to the MYB breakpoint in 6q23.3. Our study provides new knowledge about the prevalence and clinical significance of MYB/MYBL1 alterations and indicates the presence of genes with tumor suppressive functions in 6q23.3-qter that contribute to poor prognosis and short overall survival in ACC.

Original languageEnglish
Article number3691
JournalCancers
Volume14
Issue number15
DOIs
StatePublished - Aug 2022
Externally publishedYes

Keywords

  • FISH
  • MYB
  • MYBL1
  • adenoid cystic carcinoma
  • immunohistochemistry
  • prognostic biomarker
  • tumor suppressor gene

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