Cyclin D2 promoter disrupted by t(12;22)(p13;q11.2) during transformation of chronic lymphocytic leukaemia to non-Hodgkin's lymphoma

L. Qian, J. Gong, J. Liu, J. D. Broome, P. R K Koduru

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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)-λ-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-λ 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 227bp 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.

Original languageEnglish (US)
Pages (from-to)477-485
Number of pages9
JournalBritish Journal of Haematology
Volume106
Issue number2
DOIs
StatePublished - 1999

Fingerprint

Cyclin D2
B-Cell Chronic Lymphocytic Leukemia
Non-Hodgkin's Lymphoma
Chromosomes
Sequence Analysis
Immunoglobulins
DNA
Nucleic Acid Regulatory Sequences
Trisomy
Meningitis
Cytogenetics
Open Reading Frames
Molecular Biology
Clone Cells
Recurrence
Genes
Neoplasms

Keywords

  • Cyclin D2
  • Molecular cloning
  • Richter's syndrome
  • t(12;22)

ASJC Scopus subject areas

  • Hematology

Cite this

Cyclin D2 promoter disrupted by t(12;22)(p13;q11.2) during transformation of chronic lymphocytic leukaemia to non-Hodgkin's lymphoma. / Qian, L.; Gong, J.; Liu, J.; Broome, J. D.; Koduru, P. R K.

In: British Journal of Haematology, Vol. 106, No. 2, 1999, p. 477-485.

Research output: Contribution to journalArticle

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