China
Africa
Explore chapters and articles related to this topic
Pediatric Oncology
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Stephen Lowis, Rachel Cox, John Moppett, Helen Rees
Large-scale gene expression profiling has shown that ARMS tumors lacking characteristic fusion genes are molecularly and clinically indistinguishable from ERMS.46,48 This is consistent with studies that show the fusion genes confer a negative clinical prognostic value.46,49–52 Important validation of this came from analysis of outcome by fusion status in prospectively collected samples from COG trials (D9803 and D9602).47,53 Based on these studies and an increasing understanding of the functional role of the fusion proteins in RMS, future EpSSG and COG studies will use PAX-FOXO1 fusion gene status rather than histology to stratify patients.47
Minimal Residual Disease
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Jacques J. M. van Dongen, Tomasz Szczepański, Vincent H. J. van der Velden
In several hematological malignancies, chromosome aberrations can be detected and may be used as MRD-PCR target. This includes breakpoint regions of fusion genes, fusion gene transcripts, and aberrantly expressed genes (39). An advantage of using chromosome aberrations as tumor-specific PCR targets for MRD detection is their stability during the disease course. However, many hematological malignancies do not have specific chromosome aberrations, which can be detected by PCR. Nevertheless, new techniques for rapid and efficient screening of relatively large breakpoint regions, such as long-distance PCR and long-distance inverse PCR, should render such genomic breakpoint fusion sites into more feasible MRD-PCR targets (58).
Resistance Mechanisms of Tumor Cells
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Since chromosomal translocations are the hallmark of nearly all hematological tumors (a few leukemias are associated with either hyperdiploid of hypodiploid genomes), very few secondary mutations were usually identified in whole genome sequencing projects. Secondary aberrations could be diagnosed only in subpopulations, indicating that they are not necessarily driving tumor development rather than prepare the ground for selection processes (Dobbins et al., 2013; Martelli et al., 2013; Anderson et al., 2015; Bodini et al., 2015; Lindqvist et al., 2015; Stieglitz et al., 2015; Ding et al., 2017; Bolouri et al., 2018). Based on our current knowledge, the chimeric fusion genes are sufficient to cause the onset and maintenance of the different disease types (AML, ALL). Thus, these chimeric fusion genes are highly malignant when expressed in the appropriate hematopoietic (stem- or precursor cell) compartment. These fusion genes change either the epigenetic set-up and/or transcriptional profiles (e.g., MLL-r leukemias), or convert existing “physiological” into “oncogenic signaling pathways” (e.g., BCR-ABL). The latter cases can be quite successfully treated by the available TKIs (tyrosine kinase inhibitors such as Imatinib) and KIs (kinase inhibitors). The success of these novel therapies for certain patient groups has led to the term “personalized medicine,” which is based on the rational treatment of patient based on their diagnosed gene mutations (or present ‘fusion gene’).
Identification of Three Families Carrying Hb Anti-Lepore Hong Kong Variant in Guangxi, China, and Analysis of Their Hematological Data
Published in Hemoglobin, 2022
Ju Long, Feifei Gong, Lei Sun, Guangping Lai, Lihua Chen, Mingkui Peng, Chunhui Yu, Enqi Liu
In the large number of thalassemia carriers, the α-globin gene cluster (NG_000006.1) and the β-globin gene cluster (NG_000007.3) that cause thalassemia, have larger homologous segments. Therefore, there is a certain probability of forming a fusion gene. The variants in the α-globin gene cluster carrying fusion genes identified in the population in this region include HKαα, Anti-HKαα, αααanti3.7, αααanti4.2 and α fusion, and others [13]. Most of these variants lead to increased expression of specific genes. Heterozygous carriers are usually asymptomatic but when heterozygous for a pathogenic allele, this may lead to individuals with thalassemia or cause specific significant anomalies in indicators. The Hb Anti-Lepore Hong Kong causes an abnormal increase in Hb A2 level in carriers. Although this variant does not cause serious thalassemia results, the simple abnormal Hb A2 index cannot be used as a diagnostic indicator for Anti-Lepore Hong Kong, and genetic analysis is needed to verify. When Hb A2 screening is abnormal, further analysis is needed to determine the molecular biological characteristics and to provide clear genetic counseling for carriers.
Detection of an α-Globin Fusion Gene Using Real-Time Polymerase Chain Reaction-Based Multicolor Melting Curve
Published in Hemoglobin, 2020
Ai-Ping Ju, Fan Jiang, Jian Li, Xue-Wei Tang, Dong-Zhi Li
α-Thalassemia (α-thal) is caused most frequently by a deletion of one or both of the duplicated α-globin genes. The mechanism is related to the underlying molecular structure of the α-globin gene cluster [2]. Each α gene is located within a region of homology, and interrupted by short nonhomologous regions. Misalignment and reciprocal crossover between these segments at meiosis give rise to chromosomes with either single or triplicated α-globin genes. For instance, recombination between the homologous X or Z boxes of the α-globin cluster (4.2 or 3.7 kb apart) result in chromosomes with a 4.2 or 3.7 kb deletion with one α-globin gene, the most common α-thal deletions –α4.2 (leftward) and –α3.7 (rightward) [3]. Besides deletions, duplications, inversions, or other rearrangements, recombination between homologous sequences also leads to the creation of fusion genes [4]. In this study, we report the detection of an α-globin fusion gene by real-time polymerase chain reaction (qPCR)-based multicolor melting curve analysis (MMCA).
Evolution in the management of soft tissue sarcoma: classification, surgery and use of radiotherapy
Published in Expert Review of Anticancer Therapy, 2020
Angelo Paolo Dei Tos, Sylvie Bonvalot, Rick Haas
Ahmed and Abedalthagafi have argued that histomorphology is a failed technique and propose that cancers be reclassified according to molecular genetic changes, e.g. KIT mutations, BRAF mutations, ALK rearrangements, and EWS rearrangements. Gene-specific changes have been described in diverse cancers, e.g. ALK rearrangements arise in lymphomas (anaplastic T-cell, diffuse large B-cell), lung adenocarcinomas, sarcomas (inflammatory myofibroblastic, epithelioid inflammatory myofibroblastic), and Spitz nevus, a benign skin cancer [3]. However, this approach is unlikely to become the new standard for several reasons. Fusion gene products are found in unrelated entities. The association of fusion genes with cancers which differ in classification and metastatic potential is shown in Table 1. For example, the EWS-ATF1 fusion gene is found in clear cell carcinoma, an aggressive epithelial cell tumor; and also in the rare angiomatoid fibrous histiocytoma which is almost benign. Molecular genetics must therefore be evaluated in context with morphology to avoid diagnostic errors.