Frequent occurrence of large duplications at reciprocal genomic rearrangement breakpoints in multiple myeloma and other tumors
| Autor: | W. M. Kuehl, Yan W. Asmann, Anna V. Roschke, Peter Leif Bergsagel, Yulia N. Demchenko, Wei Dong Chen |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Gene Dosage Genome Integrity Repair and Replication Biology Gene dosage Proto-Oncogene Proteins c-myc 03 medical and health sciences Genes Duplicate Gene Duplication Gene duplication Genetics Humans Chromosomal inversion Gene Rearrangement Base Sequence Models Genetic Genome Human Breakpoint Chromosome Breakage Gene rearrangement 030104 developmental biology Genetic Loci Chromosome Inversion Human genome Chromosome breakage Multiple Myeloma Comparative genomic hybridization |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkw527 |
| Popis: | Using a combination of array comparative genomic hybridization, mate pair and cloned sequences, and FISH analyses, we have identified in multiple myeloma cell lines and tumors a novel and recurrent type of genomic rearrangement, i.e. interchromosomal rearrangements (translocations or insertions) and intrachromosomal inversions that contain long (1–4000 kb; median ∼100 kb) identical sequences adjacent to both reciprocal breakpoint junctions. These duplicated sequences were generated from sequences immediately adjacent to the breakpoint from at least one—but sometimes both—chromosomal donor site(s). Tandem duplications had a similar size distribution suggesting the possibility of a shared mechanism for generating duplicated sequences at breakpoints. Although about 25% of apparent secondary rearrangements contained these duplications, primary IGH translocations rarely, if ever, had large duplications at breakpoint junctions. Significantly, these duplications often contain super-enhancers and/or oncogenes (e.g. MYC) that are dysregulated by rearrangements during tumor progression. We also found that long identical sequences often were identified at both reciprocal breakpoint junctions in six of eight other tumor types. Finally, we have been unable to find reports of similar kinds of rearrangements in wild-type or mutant prokaryotes or lower eukaryotes such as yeast. |
| Databáze: | OpenAIRE |
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