- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
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.
- MeSH
- adenokarcinom genetika patologie MeSH
- antigeny diferenciační B-lymfocytární genetika MeSH
- dospělí MeSH
- fúzní onkogenní proteiny genetika MeSH
- histokompatibilita - antigeny třídy II genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránový protein 2 asociovaný s vezikuly 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
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- adjuvantní chemoterapie škodlivé účinky MeSH
- antitumorózní látky * škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- nádory * terapie MeSH
- žilní tromboembolie MeSH
- žilní trombóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- biologické markery MeSH
- cévní endotel patologie MeSH
- koagulopatie MeSH
- lidé MeSH
- nádory * MeSH
- rizikové faktory MeSH
- tromboembolie etiologie patofyziologie MeSH
- žilní trombóza * diagnóza komplikace terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND/AIM: Per literature, patients with epidermal growth factor receptor (EGFR) exon-20 insertions respond poorly to tyrosine kinase inhibitors (TKIs). This study analyzed real-world data to examine the prognostic and predictive value of these mutations. PATIENTS AND METHODS: We conducted a retrospective cohort study using Czech TULUNG Registry data, with data on multiple mutation types, collected in 2011-2020. RESULTS: We analyzed 554 (95.85%) patients with EGFR exon-19 deletions or exon-21 L858R substitutions and 24 (4.15%) patients with exon-20 insertions who received first-line high-value therapies. We summarized clinical characteristics and outcomes in all patients and by cohort. The risk of progression was statistically significantly higher (86%) in the exon-20 insertion cohort compared to the cohort with other mutations. Although not statistically significant, the risk of death was 44% higher in patients with exon-20 insertions. CONCLUSION: Advanced NSCLC patients with rare EGFR exon-20 insertions have a high risk of progression.
- MeSH
- antitumorózní látky terapeutické užití MeSH
- časové faktory MeSH
- chemorezistence MeSH
- dospělí MeSH
- erbB receptory genetika MeSH
- exony MeSH
- fenotyp MeSH
- genetická predispozice k nemoci MeSH
- inhibitory proteinkinas terapeutické užití MeSH
- inzerční mutageneze * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- nádory plic farmakoterapie genetika mortalita patologie MeSH
- nemalobuněčný karcinom plic farmakoterapie genetika mortalita patologie MeSH
- progrese nemoci MeSH
- registrace MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
