Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia

Graux, Carlos; Cools, Jan; Melotte, Cindy; Quentmeier, Hilmar; Ferrando, Adolfo A.; Levine, Ross L.; Vermeesch, Joris Robert; Stul, Michel; Dutta, Binita; Boeckx, Nancy; Bosly, André; Heimann, Pierre; Uyttebroeck, Anne; Mentens, Nele; Somers, R.; MacLeod, Roderick A.F.; Drexler, Hans; Look, A. Thomas; Gilliland, D. Gary; Michaux, Lucienne; Vandenberghe, Peter; Włodarska, Iwona; Marynen, Peter; Hagemeijer, Anne

doi:10.1038/ng1425

Cited by 375 publications

(341 citation statements)

References 24 publications

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“…HSRs manifest as a ladder-like structure of inverted repeats within chromosomes (Schwab, 1998). Extrachromosomal amplicons appear as double minutes, which can be seen using conventional cytogenetics (Hahn, 1993), and episomes (B250 bp in length), which are only detectable using molecular biology methods (Maurer et al, 1987;Graux et al, 2004). HSRs, double minutes and episomes may contain fused genetic material from different chromosomal loci (Guan et al, 1994;Graux et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…Extrachromosomal amplicons appear as double minutes, which can be seen using conventional cytogenetics (Hahn, 1993), and episomes (B250 bp in length), which are only detectable using molecular biology methods (Maurer et al, 1987;Graux et al, 2004). HSRs, double minutes and episomes may contain fused genetic material from different chromosomal loci (Guan et al, 1994;Graux et al, 2004). Models for pathways that result in gene amplification have been reviewed in detail by Myllykangas and Knuutila (2006).…”

Section: Introductionmentioning

confidence: 99%

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DNA copy number amplification profiling of human neoplasms

et al. 2006

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DNA copy number amplifications activate oncogenes and are hallmarks of nearly all advanced tumors. Amplified genes represent attractive targets for therapy, diagnostics and prognostics. To investigate DNA amplifications in different neoplasms, we performed a bibliomics survey using 838 published chromosomal comparative genomic hybridization studies and collected amplification data at chromosome band resolution from more than 4500 cases. Amplification profiles were determined for 73 distinct neoplasms. Neoplasms were clustered according to the amplification profiles, and frequently amplified chromosomal loci (amplification hot spots) were identified using computational modeling. To investigate the site specificity and mechanisms of gene amplifications, colocalization of amplification hot spots, cancer genes, fragile sites, virus integration sites and gene size cohorts were tested in a statistical framework. Amplification-based clustering demonstrated that cancers with similar etiology, cell-oforigin or topographical location have a tendency to obtain convergent amplification profiles. The identified amplification hot spots were colocalized with the known fragile sites, cancer genes and virus integration sites, but global statistical significance could not be ascertained. Large genes were significantly overrepresented on the fragile sites and the reported amplification hot spots. These findings indicate that amplifications are selected in the cancer tissue environment according to the qualitative traits and localization of cancer genes.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DNA copy number amplification profiling of human neoplasms

et al. 2006

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“…The BCR-Abl and Abl-NUP24 fusion proteins derived from chromosomal translocation have constant tyrosine kinase activity in the absence of growth factors, and these oncogenic proteins constitutively activate Abl down-stream signal cascades, resulting in leukemia and genesis of the TME [24][25][26].…”

Section: Oncogenic Nonreceptor Protein Kinasesmentioning

confidence: 99%

Deciphering the Key Features of Malignant Tumor Microenvironment for Anti-cancer Therapy

Shang

Zhang

Pan

et al. 2012

Cancer Microenvironment

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Tumor microenvironment (TME) is important in tumor development and may be a target for anti-cancer therapy. The genesis of TME is a dynamic process that is regulated by intrinsic and extrinsic factors and coordinated by multiple genes, cells, and signal pathways. Cancer anaerobic metabolism and various oncogenes may stimulate the genesis of TME. Tumor cells and cancer stem cells actively participate in the genesis of the cancer stem cell niche and tumor neovascularization, important in the initiation of the TME. Various cancer-associated stromal cells, derived niche factors, and tumor-associated macrophages may function as promoters in the genesis of the TME. Dicer1 gene-deleted stromal cells can induce generation of cancer stem cells and initiate tumorigenesis, suggesting that stromal cells also may promote the genesis of the TME. Therefore, the key features of TME include niche-driving oncogenes, cancer anaerobic metabolism, niche-driving cancer stem cells, neovascularization, tumor-associated inflammatory cells, and cancer-associated stromal cells. These features are potential targets for normalization of the malignant TME and effective anti-cancer therapy.

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“…63 The second most frequent and biologically distinct ABL1 fusion gene is NUP214-ABL1. 64 Remarkably, this fusion is generated by circularization of the 500-kb genomic region from ABL1 to NUP214 and subsequent extrachromosomal (episomal) amplification. The fusion is cryptic cytogenetically and to date remains the only example of gene fusion by episome formation in malignancy.…”

Section: Tk Fusion Genes Involving Abl1mentioning

confidence: 99%