title: Silenced expression of NFKBIA in lung adenocarcinoma patients with a never-smoking history.
abstract: Nuclear factor of κ-light polypeptide gene enhancer in B cells inhibitor α (NFKBIA), which is a tumor suppressor gene, was found to be silenced in lung adenocarcinomas. We examined NFKBIA expression, mutations in the EGFR and K-ras genes, and EML4-ALK fusion in 101 resected lung adenocarcinoma samples from never-smokers. NFKBIA expression was evaluated using immunohistochemistry. NFKBIA expression was negative in 16 of the 101 samples (15.8%). EGFR and K-ras mutations and EML4-ALK fusion were detected in 61 (60.5%), 1 (1.0%), and 2 (2.0%) of the 101 samples, respectively, in a completely mutually exclusive manner. Negative NFKBIA expression was observed significantly more frequently among the tumors with none of the three genetic alterations compared to those with such alterations (p = 0.009). In addition, negative NFKBIA expression was significantly more frequent among the EGFR-wild type samples compared to the EGFR-mutant samples (p = 0.013). In conclusion, NFKBIA expression was silenced in adenocarcinomas without EGFR/K-ras mutations or EML4-ALK fusion, suggesting that the silencing of NFKBIA may play an important role in the carcinogenesis of adenocarcinomas independent of EGFR/K-ras mutations or EML4-ALK fusion.
authors: Department of Thoracic Surgery, Okayama University Hospital, Okayama 700-8558, Japan.
authors: Masashi
authors: M
authors: Furukawa
authors: Junichi
authors: J
authors: Soh
authors: Hiromasa
authors: H
authors: Yamamoto
authors: Kouichi
authors: K
authors: Ichimura
authors: Kazuhiko
authors: K
authors: Shien
authors: Yuho
authors: Y
authors: Maki
authors: Takayuki
authors: T
authors: Muraoka
authors: Norimitsu
authors: N
authors: Tanaka
authors: Tsuyoshi
authors: T
authors: Ueno
authors: Hiroaki
authors: H
authors: Asano
authors: Kazunori
authors: K
authors: Tsukuda
authors: Shinichi
authors: S
authors: Toyooka
authors: Shinichiro
authors: S
authors: Miyoshi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D020868:Gene Silencing; D006801:Humans; D020672:I-kappa B Proteins / Q000032:analysis / Q000235:genetics*; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000072000:NF-KappaB Inhibitor alpha; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012907:Smoking / Q000009:adverse effects; D018631:ras Proteins / Q000235:genetics
chemical_list: C522504:EML4-ALK fusion protein, human; D020672:I-kappa B Proteins; C117307:KRAS protein, human; C000606204:NFKBIA protein, human; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D000072000:NF-KappaB Inhibitor alpha; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins