A FISH assay efficiently screens for BRAF gene rearrangements in pancreatic acinar-type neoplasms Journal Article
| Authors: | Wang, L.; Basturk, O.; Wang, J.; Benayed, R.; Middha, S.; Zehir, A.; Linkov, I.; Rao, M.; Aryeequaye, R.; Cao, L.; Chmielecki, J.; Ross, J.; Stephens, P. J.; Adsay, V.; Askan, G.; Balci, S.; Klimstra, D. S. |
| Article Title: | A FISH assay efficiently screens for BRAF gene rearrangements in pancreatic acinar-type neoplasms |
| Abstract: | Approximately 1-2% of pancreatic neoplasms are acinar cell carcinomas. Recently, BRAF gene rearrangements were identified in over 20% of acinar-type neoplasms, which included both pure acinar cell carcinomas and mixed carcinomas with acinar differentiation, using next-generation sequencing-based platforms, providing a potential therapeutic target for patients with these neoplasms. Thus, it is clinically important to develop a rapid, cost- and material-efficient assay to screen for BRAF gene fusions in pancreatic acinar-type neoplasms. We developed a dual color, break-apart FISH assay to detect BRAF gene rearrangements in these neoplasms and evaluated its performance in comparison to next-generation sequencing-based studies. A blinded BRAF rearrangement FISH investigation was performed on 31 acinar-type neoplasms that had been studied previously by next-generation sequencing-based analysis as well as on 18 additional acinar-type neoplasms that were accrued over the past 2 years. In total, BRAF fusions were identified in 12/49 (24%) acinar-type neoplasms by FISH. BRAF fusion partners were uncovered by using targeted next-generation sequencing studies in 11 FISH-positive cases that had sufficient material for next-generation sequencing studies. SND1 was the most frequent fusion partner involved in BRAF-fusion acinar-type neoplasms (50%), followed by HERPUD1 (18%). No BRAF fusions were identified by next-generation sequencing in any of the FISH-negative cases investigated. FISH analysis showed that BRAF rearrangements were diffusely present across tumor-rich areas in BRAF-fusion acinar-type neoplasms, which is consistent with an oncogenic driver alteration pattern. Thus, we demonstrated that, in comparison to targeted next-generation sequencing-based technologies, the FISH assay is highly sensitive and specific as well as time- and cost-efficient in the detection of BRAF fusions in acinar-type neoplasms. The FISH assay can be easily implemented in diagnostic settings to identify acinar-type neoplasms patients potentially suitable for targeted therapy to inhibit MAPK pathway activity. © 2018 USCAP, Inc All rights reserved. |
| Keywords: | adolescent; adult; clinical article; aged; histopathology; comparative study; fluorescence in situ hybridization; gene rearrangement; clinical evaluation; gene fusion; acinar cell carcinoma; genetic screening; b raf kinase; next generation sequencing; human; male; female; priority journal; article |
| Journal Title: | Modern Pathology |
| Volume: | 31 |
| Issue: | 1 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2018-01-01 |
| Start Page: | 132 |
| End Page: | 140 |
| Language: | English |
| DOI: | 10.1038/modpathol.2017.106 |
| PROVIDER: | scopus |
| PUBMED: | 28884748 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2018 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work