title: Mutations in the RAD54 recombination gene in primary cancers.
abstract: Association of a recombinational repair protein RAD51 with tumor suppressors BRCA1 and BRCA2 suggests that defects in homologous recombination are responsible for tumor formation. Also recent findings that a protein associated with the MRE11/RAD50 repair complex is mutated in Nijmegen breakage syndrome characterized by increased cancer incidence and ionizing radiation sensitivity strongly support this idea. However, the direct roles of BRCA proteins and the protein responsible for NBS in recombinational repair are not clear though they are associated with the recombinational repair complexes. Since RAD51 forms a complex with other members of the RAD52 epistasis group and with BRCA proteins, it is reasonable to ask if alterations of members of the RAD52 epistasis group lead to tumor development. Here we describe missense mutations at functional regions of RAD54 and the absence of the wild-type RAD54 expression resulting from aberrant splicing in primary cancers. Since RAD54 is a recombinational protein associated with RAD51, this is the first genetic evidence that cancer arises from a defect in repair processes involving homologous recombination.
authors.affiliation: Department of Molecular Pathology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Matsuda
authors.forename: K
authors.initials: K
authors.lastname: Miyagawa
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Fukuda
authors.forename: T
authors.initials: T
authors.lastname: Kataoka
authors.forename: T
authors.initials: T
authors.lastname: Asahara
authors.forename: H
authors.initials: H
authors.lastname: Inui
authors.forename: M
authors.initials: M
authors.lastname: Watatani
authors.forename: M
authors.initials: M
authors.lastname: Yasutomi
authors.forename: N
authors.initials: N
authors.lastname: Kamada
authors.forename: K
authors.initials: K
authors.lastname: Dohi
authors.forename: K
authors.initials: K
authors.lastname: Kamiya
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000368:Aged; D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics*; D017124:Conserved Sequence; D004265:DNA Helicases; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D008223:Lymphoma / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D004265:DNA Helicases; C103532:RAD54L protein, human