A FISH assay efficiently screens for BRAF gene rearrangements in pancreatic acinar-type neoplasms
| Autor: | Volkan Adsay, Long Cao, Gokce Askan, Ruth Aryeequaye, Ahmet Zehir, Serdar Balci, Juliann Chmielecki, Mamta Rao, Ryma Benayed, David S. Klimstra, Olca Basturk, Irina Linkov, Philip J. Stephens, Lu Wang, Jeffrey S. Ross, Sumit Middha, Jiajing Wang |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Proto-Oncogene Proteins B-raf 0301 basic medicine SND1 Adolescent medicine.medical_treatment In situ hybridization Biology Pathology and Forensic Medicine Targeted therapy Young Adult 03 medical and health sciences 0302 clinical medicine Carcinoma medicine Acinar cell Humans Gene In Situ Hybridization Fluorescence Aged Aged 80 and over Gene Rearrangement Carcinoma Acinar Cell Gene Expression Profiling Gene rearrangement Middle Aged medicine.disease Molecular biology Pancreatic Neoplasms 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Fish Female |
| Zdroj: | Modern Pathology. 31:132-140 |
| ISSN: | 0893-3952 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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