Identification of tumors with NRG1 rearrangement, including a novel putative pathogenic UNC5D-NRG1 gene fusion in prostate cancer by data-drilling a de-identified tumor database
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články
PubMed
33583086
DOI
10.1002/gcc.22942
Knihovny.cz E-zdroje
- Klíčová slova
- EGF-like domain, ERBB, ERBB3, HER, HER 3, MAPK, NRG1, PIK, carcinoma, data drilling, gene fusion, gene rearrangement, genetics, lung, mRNA sequencing, molecular, neuregulin, next-generation sequencing, receptor heterodimerization, receptor tyrosine kinase,
- MeSH
- adenokarcinom genetika patologie MeSH
- antigeny diferenciační B-lymfocytární genetika MeSH
- dospělí MeSH
- fúzní onkogenní proteiny genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránový protein 2 asociovaný s vezikuly genetika MeSH
- MHC antigeny II. třídy genetika MeSH
- nádory plic genetika patologie MeSH
- nádory prostaty genetika patologie MeSH
- neuregulin-1 genetika MeSH
- receptory buněčného povrchu genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- syndekan-4 genetika MeSH
- tenascin genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antigeny diferenciační B-lymfocytární MeSH
- fúzní onkogenní proteiny MeSH
- invariant chain MeSH Prohlížeč
- membránový protein 2 asociovaný s vezikuly MeSH
- MHC antigeny II. třídy MeSH
- neuregulin-1 MeSH
- NRG1 protein, human MeSH Prohlížeč
- receptory buněčného povrchu MeSH
- SDC4 protein, human MeSH Prohlížeč
- syndekan-4 MeSH
- tenascin MeSH
- TNC protein, human MeSH Prohlížeč
- UNC5D protein, human MeSH Prohlížeč
- VAMP2 protein, human MeSH Prohlížeč
The fusion genes containing neuregulin-1 (NRG1) are newly described potentially actionable oncogenic drivers. Initial clinical trials have shown a positive response to targeted treatment in some cases of NRG1 rearranged lung adenocarcinoma, cholangiocarcinoma, and pancreatic carcinoma. The cost-effective large scale identification of NRG1 rearranged tumors is an open question. We have tested a data-drilling approach by performing a retrospective assessment of a de-identified molecular profiling database of 3263 tumors submitted for fusion testing. Gene fusion detection was performed by RNA-based targeted next-generation sequencing using the Archer Fusion Plex kits for Illumina (ArcherDX Inc., Boulder, CO). Novel fusion transcripts were confirmed by a custom-designed RT-PCR. Also, the aberrant expression of CK20 was studied immunohistochemically. The frequency of NRG1 rearranged tumors was 0.2% (7/3263). The most common histologic type was lung adenocarcinoma (n = 5). Also, renal carcinoma (n = 1) and prostatic adenocarcinoma (n = 1) were found. Identified fusion partners were of a wide range (CD74, SDC4, TNC, VAMP2, UNC5D), with CD74, SDC4 being found twice. The UNC5D is a novel fusion partner identified in prostate adenocarcinoma. There was no co-occurrence with the other tested fusions nor KRAS, BRAF, and the other gene mutations specified in the applied gene panels. Immunohistochemically, the focal expression of CK20 was present in 2 lung adenocarcinomas. We believe it should be considered as an incidental finding. In conclusion, the overall frequency of tumors with NRG1 fusion was 0.2%. All tumors were carcinomas. We confirm (invasive mucinous) lung adenocarcinoma as being the most frequent tumor presenting NRG1 fusion. Herein novel putative pathogenic gene fusion UNC5D-NRG1 is described. The potential role of immunohistochemistry in tumor identification should be further addressed.
2nd Faculty of Medicine Charles University Prague Czech Republic
Department of Clinical Oncology Na Homolce Hospital Prague Czech Republic
Department of Oncology Hospital České Budějovice České Budějovice Czech Republic
Department of Pathology FiHM Centro Integral Oncológico Hospital de Madrid Clara Campal Madrid Spain
Department of Pathology Medical Faculty in Pilsen Charles University Prague Pilsen Czech Republic
Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University Brno Czech Republic
Molecular Genetics Department Bioptická Laboratoř s r o Pilsen Czech Republic
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