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      Fusion genes in solid tumors: an emerging target for cancer diagnosis and treatment

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          Abstract

          Studies over the past decades have uncovered fusion genes, a class of oncogenes that provide immense diagnostic and therapeutic advantages because of their tumor-specific expression. Originally associated with hemotologic cancers, fusion genes have recently been discovered in a wide array of solid tumors, including sarcomas, carcinomas, and tumors of the central nervous system. Fusion genes are attractive as both therapeutic targets and diagnostic tools due to their inherent expression in tumor tissue alone. Therefore, the discovery and elucidation of fusion genes in various cancer types may provide more effective therapies in the future for cancer patients.

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          Most cited references76

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          RET, ROS1 and ALK fusions in lung cancer.

          Through an integrated molecular- and histopathology-based screening system, we performed a screening for fusions of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1, receptor tyrosine kinase (ROS1) in 1,529 lung cancers and identified 44 ALK-fusion-positive and 13 ROS1-fusion-positive adenocarcinomas, including for unidentified fusion partners for ROS1. In addition, we discovered previously unidentified kinase fusions that may be promising for molecular-targeted therapy, kinesin family member 5B (KIF5B)-ret proto-oncogene (RET) and coiled-coil domain containing 6 (CCDC6)-RET, in 14 adenocarcinomas. A multivariate analysis of 1,116 adenocarcinomas containing these 71 kinase-fusion-positive adenocarcinomas identified four independent factors that are indicators of poor prognosis: age ≥ 50 years, male sex, high pathological stage and negative kinase-fusion status.
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            Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours.

            Ewing's sarcoma and related subtypes of primitive neuroectodermal tumours share a recurrent and specific t(11;22) (q24;q12) chromosome translocation, the breakpoints of which have recently been cloned. Phylogenetically conserved restriction fragments in the vicinity of EWSR1 and EWSR2, the genomic regions where the breakpoints of chromosome 22 and chromosome 11 are, respectively, have allowed identification of transcribed sequences from these regions and has indicated that a hybrid transcript might be generated by the translocation. Here we use these fragments to screen human complementary DNA libraries to show that the translocation alters the open reading frame of an expressed gene on chromosome 22 gene by substituting a sequence encoding a putative RNA-binding domain for that of the DNA-binding domain of the human homologue of murine Fli-1.
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              Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining.

              J D Rowley (1973)
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                Author and article information

                Journal
                Chin J Cancer
                Chin J Cancer
                CJC
                Chinese Journal of Cancer
                Sun Yat-sen University Cancer Center
                1000-467X
                1944-446X
                November 2013
                : 32
                : 11
                : 594-603
                Affiliations
                [1 ]Department of Pathology, Unit 85, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
                [2 ]The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
                Author notes
                Corresponding Author: Wei Zhang, Department of Pathology, Unit 85, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. Tel: +1-713-745-1103; Fax: +1-713-792-5549; Email: wzhang@ 123456mdanderson.org .
                Article
                cjc-32-11-594
                10.5732/cjc.013.10178
                3845546
                24206917
                369477fc-a450-4e8e-8bcd-2d2158aa5ffa
                Chinese Journal of Cancer

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission.

                History
                : 8 October 2013
                : 10 October 2013
                Categories
                Review

                tumorigenesis,therapy,chromosomal instability,cancer genomics,fusion genes

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