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

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

Author information

1
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
2
Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
3
Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
4
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
5
Department of Thoracic/Head and Neck Medicine Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
6
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
7
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas. anaggar@mdanderson.org ccaulin@mdanderson.org.
8
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas. anaggar@mdanderson.org ccaulin@mdanderson.org.

Abstract

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.

PMID:
26631609
PMCID:
PMC4807116
DOI:
10.1158/1078-0432.CCR-15-2867-T
[Indexed for MEDLINE]
Free PMC Article

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