title: Germline mutations in Dok1 do not predispose to chronic lymphocytic leukemia.
abstract: The genetic basis of familial CLL is poorly understood and to date no gene which when mutated in the germline has been unambiguously shown to confer susceptibility to the disease. Dok1 maps to chromosome 2p13, a region commonly rearranged in CLL. Dok1 inhibits MAP kinase activity, down-regulates cell proliferation and has a suppressive effect on cellular transformation and B-cell signalling pathways. A recent report has implicated mutation of Dok1 in the aetiology of CLL. To examine the proposition that germline mutations in Dok1 act as high penetrance susceptibility alleles for CLL we screened 140 familial cases for functional sequence variants. No pathogenic mutations were detected. This result indicates that germline mutations in Dok1 are unlikely to cause an inherited predisposition to CLL.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM25NG, UK.
authors.forename: G S
authors.initials: GS
authors.lastname: Sellick
authors.forename: R J
authors.initials: RJ
authors.lastname: Coleman
authors.forename: R V
authors.initials: RV
authors.lastname: Talaban
authors.forename: C
authors.initials: C
authors.lastname: Fleischmann
authors.forename: M F
authors.initials: MF
authors.lastname: Rudd
authors.forename: R
authors.initials: R
authors.lastname: Allinson
authors.forename: D
authors.initials: D
authors.lastname: Catovsky
authors.forename: R S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D000328:Adult; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C489560:DOK1 protein, human; D010750:Phosphoproteins; D016601:RNA-Binding Proteins