title: Somatic mutations of the KEAP1 gene in common solid cancers.
abstract: OBJECTIVE
  KEAP1 inhibits nuclear factor erythroid 2-related factor 2 (NRF2)-induced cytoprotection, and is considered to be a candidate tumour suppressor. Somatic mutation of NRF2 has been analysed in a wide variety of human cancers, whereas somatic mutation of KEAP1 has been reported only in lung and gall bladder cancers. The aim of our study was to investigate whether KEAP1 mutations are widespread in human cancers.
  
  
  RESULTS
  We analysed 499 cancer tissues from lung, breast, colon, stomach, liver, larynx and prostate, and leukaemias, by single-strand conformation polymorphism analysis. We detected somatic mutations of KEAP1 in gastric (11.1%), hepatocellular (8.9%), colorectal (7.8%), lung (4.6%), breast (2.0%) and prostate (1.3%) carcinomas. Allelic losses of the KEAP1 locus were identified in 42.9% of cancers with KEAP1 mutations, but no NRF2 mutations were detected in these cancers. The NRF2-activated cytoprotective proteins (NAD(P)H dehydrogenase quinone 1 and glutamine-cysteine ligase catalytic subunit) were expressed in all of the cancers with KEAP1 mutations.
  
  
  CONCLUSIONS
  Our data show that KEAP1 mutations occur widely in solid cancers, irrespective of histological type. Biallelic inactivation of KEAP1 and increased levels of cytoprotective proteins in the cancers suggest that KEAP1 mutations might protect cancer cells from oxidative insults and play a role in the development of solid cancers.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Nam Jin
authors.initials: NJ
authors.lastname: Yoo
authors.forename: Hyung Ran
authors.initials: HR
authors.lastname: Kim
authors.forename: Yoo Ri
authors.initials: YR
authors.lastname: Kim
authors.forename: Chang Hyeok
authors.initials: CH
authors.lastname: An
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D019656:Loss of Heterozygosity; D008297:Male; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1