title: Increased NRF2 gene (NFE2L2) copy number correlates with mutations in             lung squamous cell carcinomas.
abstract: Nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a transcription factor belonging to the cap 'n' collar subfamily of the basic-leucine zipper (bZIP) family of transcription factors, which plays a significant role in adaptive responses to oxidative stress. Previously, we reported that NRF2 gene (NFE2L2) mutations correlate with poor prognosis of lung squamous cell carcinomas. We therefore hypothesized that an increased NRF2 gene copy number may correlate with clinicopathological features in lung cancer patients. In this study, the increased copy number of the NRF2 gene was analyzed by real-time polymerase chain reaction (real-time-PCR) amplifications in 90 surgically-treated non-small cell lung cancer (NSCLC) cases. In total, 16 NRF2 mutation cases were included. An increased NRF2 gene copy number was found in 7 (7.8%) lung squamous cell carcinoma patients. Increased NRF2 copy number status significantly correlated with mutation status (mutant, 31.25% vs. wild-type, 2.7%; p=0.0017). The mean NRF2 gene copy number was significantly higher in mutant (2.478 ± 0.668) compared to wild-type NRF2 (1.917 ± 0.737) (p=0.0048). However, the copy number did not correlate with smoking status (p=0.3741), gender (p=0.1545), age (≥65 vs. <65, p=0.1237) and pathological stage. Although an increased NRF2 copy number correlates with mutations in squamous cell carcinoma, the percentage of the increased copy number was low; therefore, another mechanism may exist for the activation of NRF2 mutations in cancer.
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. hisasaki @med.nagoya-cu.ac.jp
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shitara
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yokota
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
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D005260:Female; D018628:Gene Dosage; D015894:Genome, Human; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012907:Smoking / Q000235:genetics; D018709:Statistics, Nonparametric
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human