Abstract:
UNLABELLED: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.
journal_name
Cancer Discovjournal_title
Cancer discoveryauthors
Brayer KJ,Frerich CA,Kang H,Ness SAdoi
10.1158/2159-8290.CD-15-0859subject
Has Abstractpub_date
2016-02-01 00:00:00pages
176-87issue
2eissn
2159-8274issn
2159-8290pii
2159-8290.CD-15-0859journal_volume
6pub_type
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