title: Germline mutations in RAD51, RAD51AP1, RAD51B, RAD51C,RAD51D, RAD52 and RAD54L do not contribute to familial chronic lymphocytic leukemia.
abstract: While familial predisposition to B-cell chronic lymphocytic leukemia (CLL) is well recognized no gene which when mutated in the germline has been unambiguously shown to confer susceptibility to the disease. An approach based on mutation screening methods targeted to coding regions of candidate genes offers an attractive strategy for the identification of rare disease-causing alleles. The RAD genes participate in the cellular response to DNA double strand breaks, detecting DNA damage, activating cell cycle checkpoints and apoptosis. Defects in members of these genes are linked to increased chromosomal instability and in lymphoma predisposition, thereby representing strong candidate susceptibility genes a priori. To examine this proposition we screened 75 familial CLL probands for germline mutations in this set of genes. No overt pathogenic mutations were identified. These findings indicate that germline mutations in RAD51, RAD51AP1, RAD51L1, RAD51L3, RAD52 and RAD54L are unlikely to be causal of an inherited predisposition to CLL.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Sellick
authors.forename: Sarah
authors.initials: S
authors.lastname: Fielding
authors.forename: Mobshra
authors.initials: M
authors.lastname: Qureshi
authors.forename: Daniel
authors.initials: D
authors.lastname: Catovsky
authors.forename: Richard
authors.initials: R
authors.lastname: Houlston
mesh_terms: D004265:DNA Helicases; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins; D051135:Rad51 Recombinase / Q000235:genetics*; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C110410:RAD51AP1 protein, human; C413002:RAD51B protein, human; C448305:RAD51C protein, human; C112629:RAD51D protein, human; C497194:RAD52 protein, human; D016601:RNA-Binding Proteins; D051721:Rad52 DNA Repair and Recombination Protein; D051135:Rad51 Recombinase; D004265:DNA Helicases; C103532:RAD54L protein, human