HRAS, EGFR, MET, and RON Genes Are Recurrently Activated by Provirus Insertion in Liver Tumors Induced by the Retrovirus Myeloblastosis-Associated Virus 2

0486763 - ÚMG 2018 RIV US eng J - Journal Article
Pečenka, Vladimír - Pajer, Petr - Karafiát, Vít - Kašparová, P. - Dudlová, J. - Dvořák, Michal
HRAS, EGFR, MET, and RON Genes Are Recurrently Activated by Provirus Insertion in Liver Tumors Induced by the Retrovirus Myeloblastosis-Associated Virus 2.
Journal of Virology. Roč. 91, č. 20 (2017), č. článku e00467-17. ISSN 0022-538X. E-ISSN 1098-5514
R&D Projects: GA MŠMT LO1419; GA ČR GA301/09/1727
Institutional support: RVO:68378050
Keywords : avian tetroviruses * insertional mutagenesis * retroviral oncogenesis
OECD category: Virology
Impact factor: 4.368, year: 2017

Myeloblastosis-associated virus 2 (MAV-2) is a highly tumorigenic simple avian retrovirus. Chickens infected in ovo with MAV-2 develop tumors in the kidneys, lungs, and liver with a short latency, less than 8 weeks. Here we report the results of molecular analyses of MAV-2-induced liver tumors that fall into three classes: hepatic hemangiosarcomas (HHSs), intrahepatic cholangiocarcinomas (ICCs), and hepatocellular carcinomas (HCCs). Comprehensive inverse PCR-based screening of 92 chicken liver tumors revealed that in ca. 86% of these tumors, MAV-2 provirus had integrated into one of four gene loci: HRAS, EGFR, MET, and RON. Insertionally mutated genes correlated with tumor type: HRAS was hit in HHSs, MET in ICCs, RON mostly in ICCs, and EGFR mostly in HCCs. The provirus insertions led to the overexpression of the affected genes and, in the case of EGFR and RON, also to the truncation of exons encoding the extracellular ligand-binding domains of these transmembrane receptors. The structures of truncated EGFR and RON closely mimic the structures of oncogenic variants of these genes frequently found in human tumors (EGFRvIII and sfRON).
Permanent Link: http://hdl.handle.net/11104/0281495