title: Mutated ephrin receptor genes in non-small cell lung carcinoma and their occurrence with driver mutations-targeted resequencing study on formalin-fixed, paraffin-embedded tumor material of 81 patients.
abstract: Non-small cell lung carcinoma (NSCLC) is the most common subtype of lung cancer. The oncogenic potential of receptor tyrosine kinases (RTKs) is widely known and they are potential targets for tailored therapy. Ephrin receptors (Ephs) form the largest group of RTKs. Nevertheless, Ephs are not widely studied in NSCLC so far. The aim of our study was to investigate novel mutations of Eph genes (EPHA1-8, EPHB1-4, EPHB6) and their association with clinically relevant mutations in BRAF, EML4-ALK, EGFR, INSR, KDR, KRAS, MET, PDGFRA, PDGFRB, PIK3, PTEN, RET, and TP53 in NSCLC patients. Targeted resequencing was conducted on 81 formalin-fixed, paraffin-embedded NSCLC tumor specimens. We analyzed missense and nonsense mutations harbored in the coding regions of the selected genes. We found 18 novel mutations of Ephs in 20% (16 of 81) of the patients. Nearly half of these mutations occurred in the protein kinase domain. The mutations were not mutually exclusive with other clinically relevant mutations. Our study shows that Ephs are frequently mutated in NSCLC patients, and occur together with other known mutations relevant to the pathogenicity of NSCLC.
authors.affiliation: Department of Pathology, Haartman Institute, University of Helsinki, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Mäki-Nevala
authors.forename: Virinder
authors.initials: V
authors.lastname: Kaur Sarhadi
authors.forename: Katja
authors.initials: K
authors.lastname: Tuononen
authors.forename: Sonja
authors.initials: S
authors.lastname: Lagström
authors.forename: Pekka
authors.initials: P
authors.lastname: Ellonen
authors.forename: Mikko
authors.initials: M
authors.lastname: Rönty
authors.forename: Aino
authors.initials: A
authors.lastname: Wirtanen
authors.forename: Aija
authors.initials: A
authors.lastname: Knuuttila
authors.forename: Sakari
authors.initials: S
authors.lastname: Knuutila
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D018389:Codon, Nonsense; D005404:Fixatives; D005557:Formaldehyde; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D020125:Mutation, Missense; D016612:Paraffin Embedding; D036081:Receptors, Eph Family / Q000235:genetics* / Q000378:metabolism
chemical_list: D018389:Codon, Nonsense; D005404:Fixatives; D005557:Formaldehyde; D036081:Receptors, Eph Family
keywords: Finnish Cancer Organizations; Pfizer Oy; The Sigrid Jusélius Foundation; and AstraZeneca AS; the special governmental subsidy research funds appropriated to the Helsinki and Uusimaa Hospital District (HUS EVO)