title: Keap1mutations in lung cancer patients.
abstract: Kelch-like ECH-associated protein 1 (Keap1) inhibits nuclear factor erythroid 2-related 2 (NEF2L2; also named NRF2)-induced cytoprotection and has been hypothesized to represent a candidate tumor suppressor. We have previously reported the somatic mutations of the NRF2 gene (NFE2L2), however, the correlation between theKeap1mutation and the clinicopathological features of lung cancer has not been well investigated. Therefore, in the present study, theKeap1mutational status in non-small cell lung cancer (NSCLC) patients was investigated by reverse transcription PCR and direct sequencing. The study included 76 surgically-removed lung cancer cases from patients of the Nagoya City University Hospital in which theEGFRandNFE2L2mutation status was already established.Keap1mutations were identified in 2 (2.6%) adenocarcinoma patients with a history of heavy smoking. These mutations were identified to exist exclusively. TheKeap1mutation was only detected in patients with advanced adenocarcinoma (4.3%) and the completely exclusive status of this mutation and others, includingEGFR,Kas,erbB2andNRF2L2,is likely to improve the selection of personalized therapy for lung cancer.
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Ayumi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shitara
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Okuda
authors.forename: Yu
authors.initials: Y
authors.lastname: Hikosaka
authors.forename: Satoru
authors.initials: S
authors.lastname: Moriyama
authors.forename: Motoki
authors.initials: M
authors.lastname: Yano
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujii
keywords: Keap1; NRF2; adenocarcinoma; lung cancer; mutations