MUC1 dysregulation as the consequence of a t(1;14)(q21;q32) translocation in an extranodal lymphoma
| Autor: | Frédéric Gilles, Yvonne Remache, Andre Goy, Peter Shue, Andrew D. Zelenetz |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Untranslated region
Lymphoma Immunology Molecular Sequence Data Restriction Mapping Locus (genetics) Chromosomal translocation Biology Biochemistry Translocation Genetic Cell Line medicine Humans Enhancer Gene In Situ Hybridization Fluorescence Genetics Chromosomes Human Pair 14 medicine.diagnostic_test Base Sequence Breakpoint Mucin-1 Ascites Chromosome Mapping Cell Biology Hematology Cosmids Immunoglobulin class switching Chromosomes Human Pair 1 Karyotyping Multigene Family Fluorescence in situ hybridization |
| Zdroj: | Blood. 95(9) |
| ISSN: | 0006-4971 |
| Popis: | Cytogenetic abnormalities at chromosome 1q21 are among the most common lesions in diffuse large-cell lymphoma and have been associated with a poor prognosis. A novel cell line, SKI-DLCL-1, was established from ascitic fluid that carries a t(1;14)(q21;q32) chromosomal translocation. Using pulsed-field gel electrophoresis, the breakpoint on the IgH locus mapped to a gamma locus between Calpha(1) and Calpha(2). A cosmid library was prepared from SKI-DLCL-1, and Cgamma-positive clones spanning the breakpoint were identified by screening with fluorescence in situ hybridization. The breakpoint occurs 860 bp downstream of the 3' UTR of the MUC1 gene. The break appears to be a staggered double-strand break consistent with an error in immunoglobulin class switching. The MUC1 gene is highly transcribed and translated, and the protein is highly glycosylated. It is postulated that MUC1 expression is brought under the control of the 3'Ealpha enhancer. MUC1 lies in a region of chromosome 1 characterized by an unusually high density of genes, with 7 known genes in a region of approximately 85 kb. To determine whether there was a pleiotropic effect of the expression of genes in the region as a consequence of the translocation, the expression of 6 additional genes was assessed. None of the other genes in this region (CLK2, propin, COTE1, GBA, metaxin, and thrombospondin 3) are overexpressed in SKI-DLCL-1. Thus, the translocation t(1;14)(q21;q32) seen in both the primary tumor and the derived cell line results in the marked overexpression of MUC1 without affecting the expression of other genes in the region. (Blood. 2000;95:2930-2936) |
| Databáze: | OpenAIRE |
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