Document Detail

Cyclin D2 promoter disrupted by t(12;22)(p13;q11.2) during transformation of chronic lymphocytic leukaemia to non-Hodgkin's lymphoma.
MedLine Citation:
PMID:  10460609     Owner:  NLM     Status:  MEDLINE    
In a unique case of chronic lymphocytic leukaemia (CLL) we performed a longitudinal cytogenetic and molecular genetic study of tumour cells from diagnosis through progression and transformation to non-Hodgkin's lymphoma (NHL) and lymphomatous meningitis. CLL cells at diagnosis had trisomy 12 and a t(14;19)(q32;q13.3). At relapse, the leukaemic cells had a subclone carrying a t(12;22)(p13;q11.2) in addition to the initial changes. We cloned reciprocal translocation junctions at the 22q11.2- chromosome and the 12p13+ chromosome and the corresponding germline DNA fragments. Restriction map analysis and nucleotide sequence analysis of the cloned DNA fragment from the 22q11.2- chromosome mapped the translocation break within the immunoglobulin (Ig)-lambda-C complex at the nt3889; nts 3890, 3891 were lost from the translocation site. A probe from the 3'-end of the clone derived from the 22q11.2- chromosome showed single copy hybridization which was different from the Ig-lambda probe. Nucleotide sequence analysis of the exact junction region and the corresponding germline DNA showed that the translocation at 12p13 occurred in the negative regulatory region of the cyclin D2 gene at the nt -1602, and a pentamer consisting of nts -1603 to -1599 was lost at the break site. We sequenced another 227 bp upstream of the known 5'-end of the promoter and did not find any open reading frame. From these results we hypothesize that, in this patient, the t(12;22) disrupted the negative regulator in the promoter of cyclin D2 which in turn might have deregulated cyclin D2.
L Qian; J Gong; J Liu; J D Broome; P R Koduru
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  British journal of haematology     Volume:  106     ISSN:  0007-1048     ISO Abbreviation:  Br. J. Haematol.     Publication Date:  1999 Aug 
Date Detail:
Created Date:  1999-10-14     Completed Date:  1999-10-14     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372544     Medline TA:  Br J Haematol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  477-85     Citation Subset:  IM    
Department of Laboratories, North Shore University Hospital, Manhasset, N.Y., USA.
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MeSH Terms
Base Sequence
Blotting, Southern
Cell Transformation, Neoplastic
Chromosomes, Human, Pair 12 / genetics*
Chromosomes, Human, Pair 22 / genetics*
Cloning, Molecular
Cyclin D2
Cyclins / genetics*
Gene Rearrangement, B-Lymphocyte, Heavy Chain
Genes, Immunoglobulin / genetics
Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
Lymphoma, Non-Hodgkin / genetics*
Molecular Sequence Data
Sequence Analysis, DNA
Translocation, Genetic / genetics*
Reg. No./Substance:
0/CCND2 protein, human; 0/Cyclin D2; 0/Cyclins

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