AI Article Synopsis
- The study investigates the role of a transcription factor in the development and progression of multiple myeloma, a type of cancer, focusing on the mechanisms of its dysregulation.* -
- In a large analysis of 1,267 newly diagnosed myeloma patients, rearrangements affecting specific genomic regions were found in 36% of cases, leading to increased expression of certain genes linked to cancer progression.* -
- The research identifies distinct mechanisms of chromosomal rearrangements in myeloma compared to lymphomas, revealing that these changes cause overexpression of critical genes, including a glucose metabolism gene influenced by a transcription factor binding at its promoter.*
Article Abstract
is a widely acting transcription factor and its deregulation is a crucial event in many human cancers. is important biologically and clinically in multiple myeloma, but the mechanisms underlying its dysregulation are poorly understood. We show that rearrangements are present in 36.0% of newly diagnosed myeloma patients, as detected in the largest set of next generation sequencing data to date (n=1,267). Rearrangements were complex and associated with increased expression of and , but not other genes at 8q24. The highest effect on gene expression was detected in cases where the locus is juxtaposed next to super-enhancers associated with genes such as and We identified three hotspots of recombination at 8q24, one of which is enriched for translocations. Breakpoint analysis indicates primary myeloma rearrangements involving the locus occur through non-homologous end joining, whereas secondary rearrangements occur through microhomology-mediated end joining. This mechanism is different to lymphomas, where non-homologous end joining generates rearrangements. Rearrangements resulted in overexpression of key genes and chromatin immunoprecipitation-sequencing identified that , a member of the glucose metabolism pathway, is directly over-expressed through binding of at its promoter.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109748 | PMC |
| http://dx.doi.org/10.3324/haematol.2019.217927 | DOI Listing |
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