title: Translocation t(2;7)(p12;q21-22) with dysregulation of the CDK6 gene mapping to 7q21-22 in a non-Hodgkin's lymphoma with leukemia.
abstract: OBJECTIVE
  A female patient presented with splenomegaly and lymphocytosis with atypical lymphoid cell morphology. We identified t(2;7)(p12;q21) prompting studies of the translocation breakpoint and its consequences on protein expression to confirm or otherwise the recently reported involvement of CDK6 and IG k genes in the t(2;7) leading to over-expression of CDK6 protein.
  
  
  METHODS
  A variety of clinical and laboratory techniques including cell marker, cytogenetic and histologic studies were applied in order to establish the diagnosis. Fluorescence in situ hybridization (FISH) and Southern blotting were used for mapping the translocation breakpoint and Western blotting for assessing protein expression.
  
  
  RESULTS
  Immunophenotyping showed the presence of a B-cell population with strong expression of FMC7, CD22, CD79b, CD5 and k restricted surface immunoglobulins. Based on morphology and immunophenotypic markers the diagnosis of B-cell non-Hodgkin's lymphoma was made. Karyotyping revealed a clone with t(2;7)(p12;q21-22). Evidence for clonal evolution with additional abnormalities including a deletion of the TP53 was present. We established by FISH and Southern blotting that the breakpoint on 7q21-22 fell in a region 66kb telomeric to the previously reported breakpoint for the t(2;7) and was the same as that observed in a t(7;21). CDK6 protein was over-expressed. The patient received alkylating agents and splenectomy and is alive but the lymphocytosis persists with evidence of disease progression.
  
  
  CONCLUSIONS
  We have demonstrated that CDK6 expression is dysregulated even when the breakpoint on 7q21-22 is located 66kb upstream from the coding region. Interestingly, the precise assignment of the lymphoma type in our case was not possible even when the splenic histology was analyzed.
authors.affiliation: FRC Path, Academic Department of Hematology and Cytogenetics, Royal Marsden NHS Trust/Institute of Cancer Research, 203, Fulham Road, London SW3 6JJ, UK. vasantha@icr.ac.uk
authors.forename: Vasantha
authors.initials: V
authors.lastname: Brito-Babapulle
authors.forename: Alicja M
authors.initials: AM
authors.lastname: Gruszka-Westwood
authors.forename: Georgina
authors.initials: G
authors.lastname: Platt
authors.forename: Claus L
authors.initials: CL
authors.lastname: Andersen
authors.forename: Manal O
authors.initials: MO
authors.lastname: Elnenaei
authors.forename: Estella
authors.initials: E
authors.lastname: Matutes
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Wotherspoon
authors.forename: Simon G
authors.initials: SG
authors.lastname: Weston-Smith
authors.forename: Daniel
authors.initials: D
authors.lastname: Catovsky
mesh_terms: D000368:Aged; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D002897:Chromosomes, Human, Pair 7; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases; D020732:Cytogenetic Analysis; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D016609:Neoplasms, Second Primary / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: D017346:Protein Serine-Threonine Kinases; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases