Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MYC locus rearrangements-often complex combinations of translocations, insertions, deletions and inversions-in multiple myeloma (MM) were thought to be a late progression event, which often did not involve immunoglobulin genes. Yet, germinal center activation of MYC expression has been reported to cause progression to MM in an MGUS (monoclonal gammopathy of undetermined significance)-prone mouse strain. Although previously detected in 16% of MM, we find MYC rearrangements in nearly 50% of MM, including smoldering MM, and they are heterogeneous in some cases. Rearrangements reposition MYC near a limited number of genes associated with conventional enhancers, but mostly with super-enhancers (e.g., IGH, IGL, IGK, NSMCE2, TXNDC5, FAM46C, FOXO3, IGJ, PRDM1). MYC rearrangements are associated with a significant increase of MYC expression that is monoallelic, but MM tumors lacking a rearrangement have biallelic MYC expression at significantly higher levels than in MGUS. We also have shown that germinal center activation of MYC does not cause MM in a mouse strain that rarely develops spontaneous MGUS. It appears that increased MYC expression at the MGUS/MM transition usually is biallelic, but sometimes can be monoallelic if there is an MYC rearrangement. Our data suggest that MYC rearrangements, regardless of when they occur during MM pathogenesis, provide one event that contributes to tumor autonomy.
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PMID:Promiscuous MYC locus rearrangements hijack enhancers but mostly super-enhancers to dysregulate MYC expression in multiple myeloma. 2451 6

Specific chromosomal abnormalities are of diagnostic and prognostic relevance as well as providing clues for the identification of causative genes in patients with hematological malignancies. Genomic array (GA) is a powerful tool for identifying both microdeletion and precise DNA breakpoints in the genes of interest. For example, GA was able to detect CDKN2A and CDKN2B deletions in a small region only 69kb in size at 9p21 that were frequently found in patients with double-hit lymphoma. Using GA combined with spectral karyotyping, fluorescence in situ hybridization, and RT-PCR, we have identified a novel PVT1 rearrangement at 8q24 which were partnered with NBEA and WWOX in multiple myeloma (MM). In patients with MM, NBEA and WWOX are frequently involved in chromosomal deletion at 13q14 and 16q23, respectively. In acute myeloid leukemia, novel fusion RNAs, PVT1-NSMCE2 and CCDC26-NSMCE2, were identified in association with marker chromosomes and double minute chromosomes derived from chromosome 8 showing 8q24 amplicons. Chromothripsis is a possible cytogenetic mechanism of generating PVT1-NSMCE2 and CCDC26-NSMCE2. As PVT1 and CCDC26 are long intergenic non-coding RNAs (lincRNAs), our study suggests that the fusion genes involving lincRNAs potentially play as-yet-unknown oncogenic functional roles. Advancements in molecular cytogenetic techniques along with next generation sequencing will facilitate the understanding of tumorigenesis in hematological malignancies.
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PMID:[Recent advancements in molecular cytogenetics for hematological malignancies: identification of novel PVT1 fusion genes]. 2645 45