PMID- 9490669
OWN - NLM
STAT- MEDLINE
DCOM- 19980409
LR  - 20220311
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 91
IP  - 6
DP  - 1998 Mar 15
TI  - Molecular cloning of translocation t(1;14)(q21;q32) defines a novel gene (BCL9) 
      at chromosome 1q21.
PG  - 1873-81
AB  - Abnormalities of chromosome 1q21 are common in B-cell malignancies and have been 
      associated with a poor response to therapy. The nature of the involved gene(s) on 
      chromosome 1q21 remains unknown. A cell line (CEMO-1) has recently been 
      established from a patient with precursor-B-cell acute lymphoblastic leukemia 
      (ALL), which exhibited a t(1;14)(q21;q32). To identify the gene involved in this 
      translocation, we have cloned both rearranged IGHJ alleles using long-distance 
      inverse polymerase chain reaction (LDI-PCR). Two IGHJ fragments were amplified 
      from CEMO-1 DNA and sequenced. One allele showed novel sequences upstream of JH5 
      with no homology to either IGH or any other sequences on the databases. Using a 
      single-copy Xho I fragment immediately 5' of JH5, PAC clones were isolated and 
      mapped to chromosome 1q21 on normal metaphases by fluorescence in situ 
      hybridization (FISH), confirming that this allele represented the 
      t(1;14)(q21;q32) breakpoint. Sequence analysis of the 1q21 Xho I fragment showed 
      identity with an expressed sequence tag (EST), and this probe was therefore used 
      to probe Northern blots. Two transcripts of 6.3 kb and 4.2 kb expressed at low 
      level in mRNA from all tissues were detected: a third transcript of 1.6 kb was 
      expressed only in thymus, spleen, and small intestine. Full-length BCL9 cDNA 
      clones were obtained from a normal human fetal brain cDNA library supplemented by 
      5' and 3' RACE. Sequence analysis predicted a protein of 1394 amino acids 
      containing 18% proline, 11% glycine, 11% serine, and 6% methionine, but no 
      recognizable protein motifs or significant homologies to any other known 
      proteins. The CEMO-1 1q21 breakpoint fell within the 3' UTR of the BCL9 gene. 
      Low-level expression of BCL9 was detected in Epstein-Barr virus-transformed 
      normal B cells by Northern blot; in contrast, abundant BCL9 expression was 
      observed in CEMO-1, indicating that deregulated expression of this gene was one 
      pathological consequence of the translocation. Screening of a panel of 39 B-cell 
      malignancies with 1q abnormalities by Southern blot showed one additional case 
      with a breakpoint in the 3' UTR of BCL9, indicating that this was a recurrent 
      breakpoint. FISH analysis using an 850-kb YAC spanning BCL9 identified a further 
      case with t(1;22)(q21;q11) causing juxtaposition of BCL9 to the IGlambda locus. 
      Other breakpoints were heterogeneous, falling both centromeric (10 cases) and 
      telomeric (10 cases) of the BCL9 gene. These data suggest that BCL9 may be the 
      target of translocation in some B-cell malignancies with abnormalities of 1q21 
      and that deregulated BCL9 expression may be important in their pathogenesis.
FAU - Willis, T G
AU  - Willis TG
AD  - Academic Department of Haematology and Cytogenetics, Institute of Cancer 
      Research, Haddow Laboratories, Sutton, Surrey, UK.
FAU - Zalcberg, I R
AU  - Zalcberg IR
FAU - Coignet, L J
AU  - Coignet LJ
FAU - Wlodarska, I
AU  - Wlodarska I
FAU - Stul, M
AU  - Stul M
FAU - Jadayel, D M
AU  - Jadayel DM
FAU - Bastard, C
AU  - Bastard C
FAU - Treleaven, J G
AU  - Treleaven JG
FAU - Catovsky, D
AU  - Catovsky D
FAU - Silva, M L
AU  - Silva ML
FAU - Dyer, M J
AU  - Dyer MJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (BCL9 protein, human)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Adult
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Blotting, Northern
MH  - Cell Line, Transformed
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 1/*genetics/*ultrastructure
MH  - Chromosomes, Human, Pair 14/*ultrastructure
MH  - Cloning, Molecular
MH  - DNA, Neoplasm/genetics
MH  - Gene Expression Regulation, Leukemic
MH  - *Genes
MH  - Humans
MH  - Male
MH  - Molecular Sequence Data
MH  - Neoplasm Proteins/biosynthesis/*genetics
MH  - Organ Specificity
MH  - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*genetics/metabolism
MH  - RNA, Messenger/biosynthesis/genetics
MH  - RNA, Neoplasm/biosynthesis/genetics
MH  - Transcription Factors
MH  - *Translocation, Genetic
EDAT- 1998/04/16 00:00
MHDA- 1998/04/16 00:01
CRDT- 1998/04/16 00:00
PHST- 1998/04/16 00:00 [pubmed]
PHST- 1998/04/16 00:01 [medline]
PHST- 1998/04/16 00:00 [entrez]
AID - S0006-4971(20)54784-8 [pii]
PST - ppublish
SO  - Blood. 1998 Mar 15;91(6):1873-81.