Molecular Cloning of Complex Chromosomal Translocation t(8;14;12)(q24.1;q32.3;q24.1) in a Burkitt Lymphoma Cell Line Defines a New Gene (BCL7A) With Homology to Caldesmon

Chromosome 12q24.1 is a recurrent breakpoint in high-grade B-cetl non-Hodgkin lymphoma (B-NHL). To identify the genes involved at 12q24.1, molecular cloning of a three-way translocation t(8;14;12)(q24.1;q32.3;q24.1) in a Burkitt lymphoma cell line (Wien 133) was performed; all four translocation bre...

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Published in:	Blood Vol. 87; no. 8; pp. 3124 - 3134
Main Authors:	Zani, V.J., Asou, N., Jadayel, D., Heward, J.M., Shipley, J., Nacheva, E., Takasuki, K., Catovsky, D., Dyer, M.J.S.
Format:	Journal Article
Language:	English
Published:	Washington, DC Elsevier Inc 15-04-1996 The Americain Society of Hematology
Subjects:	Amino Acid Sequence B-Lymphocytes - pathology Base Sequence Biological and medical sciences Burkitt Lymphoma - genetics Burkitt Lymphoma - pathology Calmodulin-Binding Proteins - genetics Chromosomes, Human, Pair 12 - genetics Chromosomes, Human, Pair 12 - ultrastructure Chromosomes, Human, Pair 14 - genetics Chromosomes, Human, Pair 14 - ultrastructure Chromosomes, Human, Pair 8 - genetics Chromosomes, Human, Pair 8 - ultrastructure Cloning, Molecular DNA, Complementary - genetics DNA, Neoplasm - genetics Gene Rearrangement, B-Lymphocyte, Heavy Chain Genes Genes, myc Hematologic and hematopoietic diseases Humans Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Lymphoma, Non-Hodgkin - genetics Lymphoma, Non-Hodgkin - pathology Medical sciences Microfilament Proteins - genetics Molecular Sequence Data Neoplasm Proteins - genetics Neoplastic Stem Cells - pathology Oncogene Proteins Oncogene Proteins, Fusion - genetics Sequence Alignment Sequence Homology, Amino Acid Tumor Cells, Cultured Chromosomal aberration Pathogenesis Homology Abnormal chromosome C8 Gene Lymphoproliferative syndrome Established cell line Genetics Molecular cloning Chromosome translocation Human Enzyme Transferases Burkitt lymphoma Exploration Malignant hemopathy B-Lymphocyte Non Hodgkin lymphoma Infection Caldesmon kinase Viral disease Gene rearrangement Abnormal chromosome Abnormal chromosome C12 Molecular biology
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Summary:	Chromosome 12q24.1 is a recurrent breakpoint in high-grade B-cetl non-Hodgkin lymphoma (B-NHL). To identify the genes involved at 12q24.1, molecular cloning of a three-way translocation t(8;14;12)(q24.1;q32.3;q24.1) in a Burkitt lymphoma cell line (Wien 133) was performed; all four translocation breakpoints were cloned and sequenced. Analysis of clones encompassing the der(12)(12;14)(q24.1;q32.3) breakpoint showed a CpG island from chromosome 12q24.l juxtaposed in a tail-to-tail configuration with a productively rearranged Ig VH4-DH-JH5 gene. A total of 4.5 kb of genomic DNA including the CpG island was sequenced and analyzed using gene-identification programs; all three programs identified a potential 92-bp exon within the centromeric boundary of the CpG island. Using this as a probe, an RNA transcript of 3.8 kb, expressed at low levels in a wide variety of normal tissues, was detected. Overlapping cDNA clones were isolated and sequenced. The longest open-reading frame predicted a serine-rich protein of 231 amino acids. This protein, termed BCL7A, exhibited no recognizable protein motifs but showed homology with the actin-binding protein, caldesmon. In Wien 133, the BCL7A breakpoint occurred within the first intron and resulted in a MYC-BCL7A fusion transcript, with exon I of BCL7A being replaced by MYC exon I. The normal, untranslocated allele of BCL7A was also expressed without mutation. One of the 11 other B-NHL cell lines examined with 12q24.1 cytogenetic abnormalities, a mediastinal B-NHL cell line (Karpas 1106), showed biallelic rearrangement within the first intron of BCL7A, which was adjacent to the breakpoint observed in Wien 133. Disruption of the amino-terminus of BCL7A defines a new mechanism in the pathogenesis of a subset of high-grade B-NHL.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0006-4971 1528-0020
DOI:	10.1182/blood.V87.8.3124.bloodjournal8783124