MYB-NFIB gene fusions identified in archival adenoid cystic carcinoma tissue employing NanoString analysis: an explorato
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RESEARCH
Open Access
MYB-NFIB gene fusions identified in archival adenoid cystic carcinoma tissue employing NanoString analysis: an exploratory study John B. McIntyre1* , Jenny J. Ko2, Jodi Siever3, Angela M. Y. Chan4, Roderick H. W. Simpson5, Desiree Hao6 and Harold Y. Lau7
Abstract Background: Adenoid cystic carcinoma (ACC) is a slow growing salivary gland malignancy that is molecularly characterized by t(6:9)(q22–23;p23–24) translocations which predominantly result in MYB-NFIB gene fusions in nearly half of tumours. Detection of MYB-NFIB transcripts is typically performed with fresh ACC tissue using conventional RT-PCR fragment analysis or FISH techniques, which are prone to failure when only archival formalin fixed paraffin embedded (FFPE) tissue is available. The purpose of this pilot study was to evaluate the utility of NanoString probe technology for the detection of MYB-NFIB transcripts in archival ACC tissue. Methods: A NanoString probeset panel was designed targeting the junctions of three currently annotated MYBNFIB fusion genes as well as 5′/3′ MYB probesets designed to detect MYB gene expression imbalance. RNA isolated from twenty-five archival ACC specimens was profiled and analyzed. RT-qPCR and sequencing were performed to confirm NanoString results. MYB protein expression was analyzed by immunohistochemistry. Results: Of the 25 samples analyzed, 11/25 (44%) expressed a high degree of MYB 5′/3′ imbalance and five of these samples were positive for at least one specific MYB-NFIB variant in our panel. MYB-NFIB variant detection on NanoString analysis was confirmed by direct cDNA sequencing. No clinical correlations were found to be associated with MYB fusion status. Conclusion: We conclude that the application of NanoString digital probe counting technology is well suited for the detection and quantification of MYB-NFIB fusion transcripts in archival ACC specimens. Keywords: Adenoid cystic carcinoma, Salivary gland, MYB, MYB-NFIB, NanoString, Fusion transcript
Background Adenoid cystic carcinoma (ACC) is a rare malignancy that can arise from head and neck sites such as salivary glands, nasopharynx, oropharynx, external ear, lacrimal gland; or other areas such as trachea, breast and female genitalia [1]. The disease is characterized by slow yet progressive tumour growth with a tendency for perineural invasion and local recurrence, often resulting in craniofacial infiltration. Primary treatment is surgical resection and/or radiotherapy however no effective systemic chemotherapeutic options are available at present * Correspondence: [email protected] 1 Translational Laboratory, Department of Oncology, University of Calgary, Calgary, AB, Canada Full list of author information is available at the end of the article
[2–4]. Early cytogenetic studies of ACC demonstrated that recurrent loss of the terminal long arm of chromosome 6 as well as reciprocal translocations of chromosomes 6q and 9p are molecular hallmarks of the disease [5]. The t(6:9)(q22–23;p23–24) translocation was subsequently shown to re
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