Targeted RNA sequencing in the routine clinical detection of fusion genes in salivary gland tumors. Issue 10 (8th July 2021)

• Record Type: Journal Article
• Authors: Bubola, Justin; MacMillan, Christina M.; Demicco, Elizabeth G.; Chami, Rose A.; Chung, Catherine T.‐S.; Leong, Iona; Marrano, Paula; Onkal, Zeynep; Swanson, David; Veremis, Brandon M.; Weinreb, Ilan; Zhang, Lei; Antonescu, Cristina R.; Dickson, Brendan C.
• Is Part Of: Genes, chromosomes & cancer. Volume 60:Issue 10(2021)
• Page Start: 695
• Page End: 708
• Publication Date: 2021-07-08
• Subjects: fusion -- RNA sequencing -- salivary gland tumor; Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22979
• Languages: English
• ISSNs: 1045-2257

Abstract

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.