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• W2505773213 abstract "Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LAIn recent years, the understanding of genomic events underlying head and neck cancer has significantly advanced. Several of the newly discovered genomic aberrations observed in salivary gland neoplasms were found to be recurrent and uniquely associated with specific disease entities. Adenoid cystic carcinoma (ACC), one of the most common salivary gland malignancies, demonstrates a particular challenge in head and neck oncology due its relentless growth, high local recurrence rate and poor long-term prognosis. Recent identification of the MYB-NFIB gene fusion as a recurrent and pathognomonic feature of ACC created new opportunities for the molecular diagnostics of this malignancy. Liquid biopsy techniques coupled with droplet digital PCR (ddPCR) platform may be feasible aiming for non-invasive detection of disease-specific genetic markers such as gene fusions. Given the prevalence of MYB-NFIB transcript in ACC, detection of the fusion event in patients’ saliva may present a unique opportunity for an accurate diagnostics as well as for long-term patient monitoring. Our goal is to develop a highly-sensitive ddPCR-based assay that would precisely detect and identify MYB-NFIB transcripts in tumor tissue and patients’ bodily fluids. RNA sequencing (RNAseq) performed in fresh frozen ACC samples identified MYB-NFIB fusion in 56% (10/18) of the cases and revealed large variability in MYB gene break sites and alternative splicing of NFIB component. 84% of ACC cases demonstrated high expression of 5’ MYB fragment by ddPCR based RT-PCR, 62.5% of which were MYB-NFIB fusion positive in RNAseq. We developed a panel of RT-PCR assays to detect a range of different MYB-NFIB transcripts observed by our RNAseq data and/or previously reported. We identified all ACC cases harboring the most commonly reported MYB-NFIB fusions (9/9) and validated the fusion products with conventional Sanger sequencing. Additionally, our preliminary results indicate that the assays are feasible for PCR multiplexing retaining the high sensitivity and specificity observed in singleplex experiments. Evaluation of the assay performance in ddPCR and assessing the detection limit is currently in progress. Once the methodology is validated, we will be able to evaluate a cohort of salivary gland neoplasms and matched RNA samples isolated from saliva. The detection of MYB-NFIB fusion in bodily fluids using a highly sensitive ddPCR platform will open a new avenue for the diagnosis and the clinical management of patients with ACC. Furthermore, our work creates the possibility of a liquid biopsy-based detection of other disease-specific gene fusions increasingly identified in different solid tumors.Citation Format: Piotr T. Wysocki, Shizhang Ling, Chunbo Shao, Marietta Tan, David Sidransky, Patrick Ha, Mariana Brait. Highly sensitive detection of MYB-NFIB fusion transcripts in adenoid cystic carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3983." @default.
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• W2505773213 date "2016-07-15" @default.
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• W2505773213 title "Abstract 3983: Highly sensitive detection of MYB-NFIB fusion transcripts in adenoid cystic carcinoma" @default.
• W2505773213 doi "https://doi.org/10.1158/1538-7445.am2016-3983" @default.
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