NUP98 Is Fused to Topoisomerase (DNA) IIβ 180 kDa (TOP2B) in a Patient with Acute Myeloid Leukemia with a New t(3;11)(p24;p15)
| Autor: | Oskar A. Haas, Helmut H. Schmidt, Sabine Strehl, Karin Nebral |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
Cancer Research Candidate gene Oncogene Proteins Fusion DNA repair Molecular Sequence Data Translocation Genetic Sequence Homology Nucleic Acid medicine Humans Gene family Amino Acid Sequence RNA Neoplasm Poly-ADP-Ribose Binding Proteins Gene In Situ Hybridization Fluorescence Genetics NUP98 Gene Base Sequence medicine.diagnostic_test biology Reverse Transcriptase Polymerase Chain Reaction Chromosomes Human Pair 11 Topoisomerase Middle Aged Molecular biology DNA-Binding Proteins Nuclear Pore Complex Proteins Non-homologous end joining DNA Topoisomerases Type II Oncology Leukemia Myeloid Acute Disease biology.protein Chromosomes Human Pair 3 Fluorescence in situ hybridization |
| Zdroj: | Clinical Cancer Research. 11:6489-6494 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-05-0150 |
| Popis: | Purpose: The nucleoporin 98 kDa (NUP98) gene has been reported to be fused to 17 different partner genes in various hematologic malignancies with 11p15 aberrations. Cytogenetic analysis of an adult de novo acute myelogenous leukemia (M5a) revealed a t(3;11)(p24;p15), suggesting rearrangement of NUP98 with a novel partner gene. Experimental Design: Fluorescence in situ hybridization (FISH) was used to confirm the involvement of NUP98 in the t(3;11)(p24;p15). Selection of possible NUP98 partner genes was done by computer-aided analysis of the 3p24 region using the University of California Santa Cruz genome browser. Fusion gene–specific FISH and reverse transcription-PCR analyses were done to verify the presence of the new NUP98 fusion. Results: FISH analysis using a NUP98-specific clone showed a split signal, indicating that the NUP98 gene was affected by the translocation. Of the genes localized at 3p24, TOP2B was selected as a possible fusion partner candidate gene. Dual-color fusion gene–specific FISH and reverse transcription-PCR analysis verified that NUP98 was indeed fused to TOP2B. In addition to reciprocal NUP98-TOP2B and TOP2B-NUP98 in-frame fusion transcripts, an alternatively spliced out-of-frame TOP2B-NUP98 transcript that resulted in a premature stop codon was detected. Analysis of the genomic breakpoints revealed typical signs of nonhomologous end joining resulting from error-prone DNA repair. Conclusions: TOP2B encodes a type II topoisomerase, which is involved in DNA transcription, replication, recombination, and mitosis, and besides TOP1, represents the second NUP98 fusion partner gene that belongs to the topoisomerase gene family. This finding emphasizes the important role of topoisomerases in malignant transformation processes. |
| Databáze: | OpenAIRE |
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