title: Inactivating mutations of KILLER/DR5 gene in gastric cancers.
abstract: OBJECTIVE
  The KILLER/death receptor (DR)5 has been identified as a potent inducer of apoptosis, and mapped to chromosome 8p21-22, showing frequent allelic loss in gastric cancer. The p53-induced apoptosis is an important biological process to prevent the development of cancer, and is mediated in part by expression of KILLER/DR5 only in cells with wild-type p53 protein, but not in those lacking p53 function. The aim of this study was to determine whether genetic alterations of KILLER/DR5 could be involved in the tumorigenesis of gastric cancer.
  
  
  METHODS
  We analyzed the genetic alterations of KILLER/DR5 and p53 in 43 gastric cancers and the loss of function of KILLER/DR5 mutants, detected in this study.
  
  
  RESULTS
  We found 3 KILLER/DR5 missense mutations (7%), and 2 of them showed allelic loss in the remaining allele. Interestingly, all the mutants inhibit apoptotic cell death in transfection studies. We also found 6 p53 mutations (14%). Interestingly, the tumors containing the KILLER/DR5 mutation did not carry the p53 mutation.
  
  
  CONCLUSIONS
  These results suggest that inactivation of KILLER/DR5 caused by mutations of KILLER/DR5 may be one of the possible escaping mechanisms against KILLER/DR5-mediated apoptosis and that inactivating mutation of KILLER/DR5 may contribute to the development or progression of a subset of gastric cancers.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea.
authors.forename: W S
authors.initials: WS
authors.lastname: Park
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: M S
authors.initials: MS
authors.lastname: Shin
authors.forename: J Y
authors.initials: JY
authors.lastname: Park
authors.forename: H S
authors.initials: HS
authors.lastname: Kim
authors.forename: Y S
authors.initials: YS
authors.lastname: Kim
authors.forename: C H
authors.initials: CH
authors.lastname: Park
authors.forename: S K
authors.initials: SK
authors.lastname: Lee
authors.forename: S H
authors.initials: SH
authors.lastname: Lee
authors.forename: S N
authors.initials: SN
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: N J
authors.initials: NJ
authors.lastname: Yoo
authors.forename: J Y
authors.initials: JY
authors.lastname: Lee
mesh_terms: D000483:Alleles; D002460:Cell Line; D004249:DNA Damage; D016158:Genes, p53; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000502:physiology; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C505639:TNFRSF10B protein, human