Targeted RNA sequencing in the routine clinical detection of fusion genes in salivary gland tumors Journal Article
| Authors: | Bubola, J.; MacMillan, C. M.; Demicco, E. G.; Chami, R. A.; Chung, C. T. S.; Leong, I.; Marrano, P.; Onkal, Z.; Swanson, D.; Veremis, B. M.; Weinreb, I.; Zhang, L.; Antonescu, C. R.; Dickson, B. C. |
| Article Title: | Targeted RNA sequencing in the routine clinical detection of fusion genes in salivary gland tumors |
| Abstract: | Salivary gland tumors represent a diverse group of neoplasms that occasionally pose a diagnostic challenge for pathologists, particularly with limited sampling. Gene fusions, which may reflect genetic drivers, are increasingly recognized in a subset of these neoplasms, and can be leveraged for diagnostic purposes. We performed a retrospective analysis on a cohort of 80 benign and malignant salivary gland tumors, enriched for subtypes known to harbor recurrent fusion events, to validate the diagnostic use of a targeted RNA sequencing assay to detect fusion transcripts. Testing identified fusion genes in 71% (24/34) of pleomorphic adenoma and carcinoma-ex-pleomorphic adenoma, with 56% of cases showing rearrangement of PLAG1 and 15% HMGA2. In addition to confirming known partners for these genes, novel PLAG1 fusion partners were identified, including DSTN, NTF3, and MEG3; CNOT2 was identified as a novel fusion partner for HMGA2. In adenoid cystic carcinoma, 95% of cases (19/20) were positive for a fusion event. MYB was rearranged in 60% (12/20), MYBL1 in 30% (6/20), and NFIB in 5% (1/20); two tumors exhibited novel fusion products, including NFIB-TBPL1 and MYBL1-VCPIP1. Fusion genes were identified in 64% (9/14) of cases of mucoepidermoid carcinoma; MAML2 was confirmed to partner with either CRTC1 (43%) or CRTC3 (21%). One salivary duct carcinoma was found to harbor a novel RAPGEF6-ACSL6 fusion gene. Finally, as anticipated, gene fusions were not detected in any of the five acinic cell carcinomas included in the cohort. In summary, targeted RNA sequencing represents a diagnostically useful ancillary technique for identifying a variety of existing, and novel, fusion transcripts in the classification of salivary gland neoplasms. © 2021 Wiley Periodicals LLC. |
| Keywords: | salivary gland tumor; fusion; rna sequencing |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 60 |
| Issue: | 10 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2021-10-01 |
| Start Page: | 695 |
| End Page: | 708 |
| Language: | English |
| DOI: | 10.1002/gcc.22979 |
| PUBMED: | 34176176 |
| PROVIDER: | scopus |
| PMCID: | PMC8753559 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 September 2021 -- Source: Scopus |
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