Recurrent Fusions in MYB and MYBL1 Define a Common, Transcription Factor-Driven Oncogenic Pathway in Salivary Gland Adenoid Cystic Carcinoma

被引:175
作者
Brayer, Kathryn J.
Frerich, Candace A.
Kang, Huining
Ness, Scott A.
机构
[1] Univ New Mexico, Hlth Sci Ctr, Dept Internal Med, Albuquerque, NM 87131 USA
[2] Univ New Mexico, Hlth Sci Ctr, UNM Comprehens Canc Ctr, Albuquerque, NM 87131 USA
关键词
DIFFERENTIAL EXPRESSION ANALYSIS; C-MYB; GENOMIC ANALYSIS; GENE FUSION; CANCER; HEAD; TARGETS; NECK; REARRANGEMENTS; TRANSLOCATION;
D O I
10.1158/2159-8290.CD-15-0859
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Adenoid cystic carcinoma (ACC), the second most common malignancy of salivary glands, is a rare tumor with a bleak prognosis for which therapeutic targets are unavailable. We used RNA sequencing (RNA-seq) to analyze low-quality RNA from archival, formaldehyde-fixed, paraffin-embedded samples. In addition to detecting the most common ACC translocation, t(6;9) fusing the MYB proto-oncogene to NFIB, we also detected previously unknown t(8; 9) and t(8; 14) translocations fusing the MYBL1 gene to the NFIB and RAD51B genes, respectively. RNA-seq provided information about gene fusions, alternative RNA splicing, and gene expression signatures. Interestingly, tumors with MYB and MYBL1 translocations displayed similar gene expression profiles, and the combined MYB and MYBL1 expression correlated with outcome, suggesting that the related MYB proteins are interchangeable oncogenic drivers in ACC. Our results provide important details about the biology of ACC and illustrate how archival tissue samples can be used for detailed molecular analyses of rare tumors. SIGNIFICANCE: Using RNA-seq to perform whole-transcriptome analysis of archival ACC tumor samples, we identified novel, recurrent gene fusions, detected alternative RNA splicing, and established gene expression signatures that provide detailed information about the biology of ACC tumors. (C) 2015 AACR.
引用
收藏
页码:176 / 187
页数:12
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