PMID- 11940479
OWN - NLM
STAT- MEDLINE
DCOM- 20020712
LR  - 20211203
IS  - 0390-6078 (Print)
IS  - 0390-6078 (Linking)
VI  - 87
IP  - 4
DP  - 2002 Apr
TI  - 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.
PG  - 357-62
AB  - BACKGROUND AND OBJECTIVES: 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. DESIGN AND 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. 
      INTERPRETATIONS AND 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.
FAU - Brito-Babapulle, Vasantha
AU  - Brito-Babapulle V
AD  - 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
FAU - Gruszka-Westwood, Alicja M
AU  - Gruszka-Westwood AM
FAU - Platt, Georgina
AU  - Platt G
FAU - Andersen, Claus L
AU  - Andersen CL
FAU - Elnenaei, Manal O
AU  - Elnenaei MO
FAU - Matutes, Estella
AU  - Matutes E
FAU - Wotherspoon, Andrew C
AU  - Wotherspoon AC
FAU - Weston-Smith, Simon G
AU  - Weston-Smith SG
FAU - Catovsky, Daniel
AU  - Catovsky D
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.22 (CDK6 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 6)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Aged
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 2
MH  - *Chromosomes, Human, Pair 7
MH  - Cyclin-Dependent Kinase 6
MH  - *Cyclin-Dependent Kinases
MH  - Cytogenetic Analysis
MH  - Female
MH  - Gene Expression Regulation
MH  - Humans
MH  - Leukemia/*genetics
MH  - Lymphoma, Non-Hodgkin/etiology/*genetics/metabolism
MH  - Neoplasms, Second Primary/genetics
MH  - Protein Serine-Threonine Kinases/*genetics/metabolism
MH  - *Translocation, Genetic
EDAT- 2002/04/10 10:00
MHDA- 2002/07/13 10:01
CRDT- 2002/04/10 10:00
PHST- 2002/04/10 10:00 [pubmed]
PHST- 2002/07/13 10:01 [medline]
PHST- 2002/04/10 10:00 [entrez]
PST - ppublish
SO  - Haematologica. 2002 Apr;87(4):357-62.