<scp>MYB</scp>,<scp>MYBL</scp>1,<scp>MYBL</scp>2 and <scp>NFIB</scp> gene alterations and <scp>MYC</scp> overexpression in salivary gland adenoid cystic carcinoma

Fujii, Kana; Murase, Takayuki; Beppu, Shintaro; Saida, Kosuke; Takino, Hisashi; Awata, Masaki; Ijichi, Kei; Kusafuka, Kimihide; Iida, Yoshiyuki; Onitsuka, Tetsuro; Yatabe, Yasushi; Hanai, Nobuhiro; Hasegawa, Yasuhisa; Inagaki, Hiroshi

doi:10.1111/his.13281

Cited by 59 publications

(62 citation statements)

References 46 publications

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“…MYBL1 was overexpressed as compared with MYB–NFIB ‐positive AdCCs and the breast cancer cell lines tested, and MYB expression was low (Figures A and B). As in a previously described MYBL1 ‐rearranged salivary gland AdCC , c‐MYB protein expression was observed (Figure A; supplementary material, Figure S2A), potentially caused by cross‐reactivity between the c‐MYB antibody and the rearranged A‐MYB protein, owing to the extensive homology between MYB and MYBL1 and their respective proteins.…”

Section: Resultssupporting

confidence: 73%

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

Kim

Geyer

Martelotto

et al. 2017

The Journal of Pathology

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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. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: Resultssupporting

confidence: 73%

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

Kim

Geyer

Martelotto

et al. 2017

The Journal of Pathology

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“…Moreover, the presence of the translocation was not associated with AdCC microscopic subtype and the presence of perineural invasion. However, Fujii et al () observed a significant association between MYB/MYBL1 split‐positive cases and positive surgical margins.…”

Section: Resultsmentioning

confidence: 99%

“…Mitani et al () observed that cases carrying MYB alterations were associated with the presence of recurrences and metastases. More recently, Fujii et al () observed that MYB/MYBL1 split‐positive cases were associated with positive microscopic surgical margins, but the authors did not investigate cases carrying only the MYB‐NFIB translocation.…”

Section: Discussionmentioning

confidence: 99%

t(6;9)(MYB‐NFIB) in head and neck adenoid cystic carcinoma: A systematic review with meta‐analysis

et al. 2019

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The presence of a translocation involving MYB and NFIB genes have been described in adenoid cystic carcinoma (AdCC) from different anatomical regions. However, the exact frequency of this genetic event and its prognostic impact for patient survival remain obscure. The aim of this study was to carry out a systematic review to address the prevalence and the prognostic potential of t(6;9)(MYB‐NFIB) in head and neck AdCC. Quantitative analysis was done to determine the prevalence of the translocation. A total of 1,107 articles were initially retrieved with 36 remaining for data extraction. The prevalence of t(6;9)(MYB‐NFIB) varied significantly (16%–100%), especially due to methodological heterogeneity among studies. A total of 11 studies attempted to determine the prognostic importance of the translocation, but no study found any significant association with survival rates; only three studies observed a significant association with age, sex, tumour location and the presence of recurrences and metastases. The prevalence of t(6;9)(MYB‐NFIB) in head and neck AdCC varies according to the laboratorial methods used, and the best evidence available demonstrates that t(6;9)(MYB‐NFIB) does not seem to be a prognostic determinant.

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“…In 2009, a fusion between the myeloblastosis ( MYB ) and nuclear factor I/B ( NFIB ) genes, resulting from t(6;9)(q22‐23;p24) translocation, was firstly identified in all 11 ACCs studied by Persson et al The fusion was found to be associated with high 5′‐MYB gene expression. MYB is an oncogene, and MYB‐NFIB gene fusion can lead to the activation of MYB and its target genes that are associated with apoptosis, cell cycle control, cell adhesion, growth, differentiation, and angiogenesis, including Proto‐Oncogene Receptor Tyrosine Kinase (KIT) , CD34 Molecule , Baculoviral IAP Repeat Containing 3(BIRC3) , MYC Proto‐Oncogene , and Mitotic Arrest Deficient Like 1 (MAD1L1) . The discovery of MYB gene fusion transcripts has revolutionized the diagnosis, surveillance, and treatment of ACC.…”

Section: Introductionmentioning

confidence: 99%

“…MYB-NFIB gene fusion can lead to the activation of MYB and its target genes that are associated with apoptosis, cell cycle control, cell adhesion, growth, differentiation, and angiogenesis, including Proto-Oncogene Receptor Tyrosine Kinase (KIT), CD34 Molecule, Baculoviral IAP Repeat Containing 3(BIRC3), MYC Proto-Oncogene, and Mitotic Arrest Deficient Like 1 (MAD1L1). [10][11][12] The discovery of MYB gene fusion transcripts has revolutionized the diagnosis, surveillance, and treatment of ACC. Recently, studies have found MYB gene fusion in patients with ACC, and NFIB has been the only consistent gene that rearranges with MYB.…”

Section: Introductionmentioning

confidence: 99%

The value of MYB as a prognostic marker for adenoid cystic carcinoma: Meta‐analysis

Liu

Chen²,

Lao

et al. 2019

Head & Neck

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The aim of this meta‐analysis is to evaluate myeloblastosis (MYB) as a prognostic marker for patients with adenoid cystic carcinoma (ACC) with respect to MYB gene fusion, MYB protein expression, and tumor sites. We comprehensively searched PubMed, Embase, Web of Science, and Cochrane libraries. Ten studies concerning the prognostic comparisons between MYB positivity and negativity were included. The combined positive rates of MYB gene fusion and protein expression were 57.2% and 62.3%, respectively. Overall, no significant prognostic differences were observed between MYB‐positive and MYB‐negative ACCs. When further divided into MYB gene fusion and MYB protein expression subgroups, no significant differences were observed for any survival outcome (overall survival, disease‐free survival, and local control rate). Moreover, MYB also demonstrated no prognostic value in head and neck ACCs. In conclusion, the current studies reveal that MYB is not a good prognostic marker for ACC.

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MYB,MYBL1,MYBL2 and NFIB gene alterations and MYC overexpression in salivary gland adenoid cystic carcinoma

Cited by 59 publications

References 46 publications

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

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

t(6;9)(MYB‐NFIB) in head and neck adenoid cystic carcinoma: A systematic review with meta‐analysis

The value of MYB as a prognostic marker for adenoid cystic carcinoma: Meta‐analysis

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