The Experts below are selected from a list of 270 Experts worldwide ranked by ideXlab platform
Kunjan S Bhakta - One of the best experts on this subject based on the ideXlab platform.
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association of ataxia telangiectasia mutated atm gene mutation deletion with Rhabdomyosarcoma
Molecular Cancer, 2003Co-Authors: Peilin Zhang, Kunjan S Bhakta, James R Feramisco, Robert O Newbury, Pier Lorenzo Puri, Jean Y. J. WangAbstract:Background Rhabdomyosarcoma is a common malignancy in children. There are two major types of Rhabdomyosarcomas, the embryonal and the alveolar, differing in cytogenetic and morphologic features. The alveolar type of Rhabdomyosarcoma is frequently associated with chromosome translocation t(2, 13) and poor clinical prognosis. Pathogenesis of Rhabdomyosarcoma remains obscure, and especially it occurs in the location where skeletal muscle is absent. We report here that there is a high frequency of association of Rhabdomyosarcoma with ataxia telangiectasia mutated (ATM) gene mutation/deletion.
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Association of Ataxia Telangiectasia Mutated (ATM) gene mutation/deletion with Rhabdomyosarcoma
Molecular Cancer, 2003Co-Authors: Peilin Zhang, Kunjan S Bhakta, James R Feramisco, Robert O Newbury, Pier Lorenzo Puri, Jean Y. J. WangAbstract:Background Rhabdomyosarcoma is a common malignancy in children. There are two major types of Rhabdomyosarcomas, the embryonal and the alveolar, differing in cytogenetic and morphologic features. The alveolar type of Rhabdomyosarcoma is frequently associated with chromosome translocation t(2, 13) and poor clinical prognosis. Pathogenesis of Rhabdomyosarcoma remains obscure, and especially it occurs in the location where skeletal muscle is absent. We report here that there is a high frequency of association of Rhabdomyosarcoma with ataxia telangiectasia mutated (ATM) gene mutation/deletion.
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association of ataxia telangiectasia mutated atm gene mutation deletion with Rhabdomyosarcoma
Cancer Biology & Therapy, 2003Co-Authors: Peilin Zhang, Kunjan S BhaktaAbstract:Background: Rhabdomyosarcoma is a common malignancy in children. There are two major types of Rhabdomyosarcomas, the embryonal and the alveolar, differing in cytogenetic and morphologic features. The alveolar type of Rhabdomyosarcoma is frequently associated with chromosome translocation t(2, 13) and poor clinical prognosis. Pathogenesis of Rhabdomyosarcoma remains obscure, and especially it occurs in the location where skeletal muscle is absent. We report here that there is a high frequency of association of Rhabdomyosarcoma with ataxia telangiectasia mutated (ATM) gene mutation/deletion. Result: Totally 17 cases of Rhabdomyosarcoma specimens were studied by immunohistochemical or immunofluorescent staining with ATM antibody and revealed that 7 of the 17 cases were negative for ATM expression (41%). Further analyses of Rhabdomyosarcoma cell lines with RT-PCR revealed that in Rh30 cells, an alveolar Rhabdomyosarcoma cell line, there are three separate deletions/mutations of the ATM mRNA. Western blotting analysis of the Rh30 cellular extract with anti-ATM antibody showed that there is an aberrant form of ATM protein within the Rh30 cells that are smaller than normal control. Conclusion: These results suggest a link of ATM gene deletion/mutation with Rhabdomyosarcoma, and since ATM kinase is a crucial regulatory protein in DNA damage repair signaling pathway, and ATM deletion/mutation may contribute to pathogenesis of Rhabdomyosarcoma.
Peilin Zhang - One of the best experts on this subject based on the ideXlab platform.
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association of ataxia telangiectasia mutated atm gene mutation deletion with Rhabdomyosarcoma
Molecular Cancer, 2003Co-Authors: Peilin Zhang, Kunjan S Bhakta, James R Feramisco, Robert O Newbury, Pier Lorenzo Puri, Jean Y. J. WangAbstract:Background Rhabdomyosarcoma is a common malignancy in children. There are two major types of Rhabdomyosarcomas, the embryonal and the alveolar, differing in cytogenetic and morphologic features. The alveolar type of Rhabdomyosarcoma is frequently associated with chromosome translocation t(2, 13) and poor clinical prognosis. Pathogenesis of Rhabdomyosarcoma remains obscure, and especially it occurs in the location where skeletal muscle is absent. We report here that there is a high frequency of association of Rhabdomyosarcoma with ataxia telangiectasia mutated (ATM) gene mutation/deletion.
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Association of Ataxia Telangiectasia Mutated (ATM) gene mutation/deletion with Rhabdomyosarcoma
Molecular Cancer, 2003Co-Authors: Peilin Zhang, Kunjan S Bhakta, James R Feramisco, Robert O Newbury, Pier Lorenzo Puri, Jean Y. J. WangAbstract:Background Rhabdomyosarcoma is a common malignancy in children. There are two major types of Rhabdomyosarcomas, the embryonal and the alveolar, differing in cytogenetic and morphologic features. The alveolar type of Rhabdomyosarcoma is frequently associated with chromosome translocation t(2, 13) and poor clinical prognosis. Pathogenesis of Rhabdomyosarcoma remains obscure, and especially it occurs in the location where skeletal muscle is absent. We report here that there is a high frequency of association of Rhabdomyosarcoma with ataxia telangiectasia mutated (ATM) gene mutation/deletion.
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association of ataxia telangiectasia mutated atm gene mutation deletion with Rhabdomyosarcoma
Cancer Biology & Therapy, 2003Co-Authors: Peilin Zhang, Kunjan S BhaktaAbstract:Background: Rhabdomyosarcoma is a common malignancy in children. There are two major types of Rhabdomyosarcomas, the embryonal and the alveolar, differing in cytogenetic and morphologic features. The alveolar type of Rhabdomyosarcoma is frequently associated with chromosome translocation t(2, 13) and poor clinical prognosis. Pathogenesis of Rhabdomyosarcoma remains obscure, and especially it occurs in the location where skeletal muscle is absent. We report here that there is a high frequency of association of Rhabdomyosarcoma with ataxia telangiectasia mutated (ATM) gene mutation/deletion. Result: Totally 17 cases of Rhabdomyosarcoma specimens were studied by immunohistochemical or immunofluorescent staining with ATM antibody and revealed that 7 of the 17 cases were negative for ATM expression (41%). Further analyses of Rhabdomyosarcoma cell lines with RT-PCR revealed that in Rh30 cells, an alveolar Rhabdomyosarcoma cell line, there are three separate deletions/mutations of the ATM mRNA. Western blotting analysis of the Rh30 cellular extract with anti-ATM antibody showed that there is an aberrant form of ATM protein within the Rh30 cells that are smaller than normal control. Conclusion: These results suggest a link of ATM gene deletion/mutation with Rhabdomyosarcoma, and since ATM kinase is a crucial regulatory protein in DNA damage repair signaling pathway, and ATM deletion/mutation may contribute to pathogenesis of Rhabdomyosarcoma.
Douglas S Hawkins - One of the best experts on this subject based on the ideXlab platform.
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dense pattern of embryonal Rhabdomyosarcoma a lesion easily confused with alveolar Rhabdomyosarcoma a report from the soft tissue sarcoma committee of the children s oncology group
American Journal of Clinical Pathology, 2013Co-Authors: Erin R Rudzinski, Julia A Bridge, Frederic G. Barr, Lisa A Teot, James R Anderson, Julie Moore, Julie M Gastierfoster, Stephen X Skapek, Douglas S HawkinsAbstract:Objectives: To examine whether the frequency of fusion-negative alveolar Rhabdomyosarcoma (ARMSn) increased coincident with changes in the definition of alveolar histology. Methods: We re-reviewed alveolar Rhabdomyosarcoma (ARMS) in the Children’s Oncology Group study D9803, comparing histopathology with fusion status. Results: Our review of 255 original ARMS cases (compared with a control group of 38 embryonal Rhabdomyosarcomas [ERMS] cases) revealed that many had an ARMS-like densely cellular pattern with cytologic features and myogenin expression more typical of ERMS. Following re-review, 84 (33%) cases of original ARMS were rediagnosed as ERMS. All reclassified ERMS, including dense ERMS, were fusion negative, whereas 82% of confirmed ARMS cases were fusion positive. Total ARMS diagnoses returned to historic rates of 25% to 30% of all Rhabdomyosarcomas, and ARMSn decreased from 37% to 18% of ARMS cases. The outcome of reclassified ERMS was similar to confirmed ERMS. Conclusions: To address the role of fusion status in risk stratification, pathologists should include both a histologic diagnosis and an evaluation of fusion status for all new ARMS diagnoses.
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comparison of genome wide binding of myod in normal human myogenic cells and Rhabdomyosarcomas identifies regional and local suppression of promyogenic transcription factors
Molecular and Cellular Biology, 2013Co-Authors: Kyle L Macquarrie, Erin R Rudzinski, Douglas S Hawkins, Zizhen Yao, Abraham P Fong, Scott J Diede, Stephen J TapscottAbstract:Rhabdomyosarcoma is a pediatric tumor of skeletal muscle that expresses the myogenic basic helix-loop-helix protein MyoD but fails to undergo terminal differentiation. Prior work has determined that DNA binding by MyoD occurs in the tumor cells, but myogenic targets fail to activate. Using MyoD chromatin immunoprecipitation coupled to high-throughput sequencing and gene expression analysis in both primary human muscle cells and RD Rhabdomyosarcoma cells, we demonstrate that MyoD binds in a similar genome-wide pattern in both tumor and normal cells but binds poorly at a subset of myogenic genes that fail to activate in the tumor cells. Binding differences are found both across genomic regions and locally at specific sites that are associated with binding motifs for RUNX1, MEF2C, JDP2, and NFIC. These factors are expressed at lower levels in RD cells than muscle cells and rescue myogenesis when expressed in RD cells. MEF2C is located in a genomic region that exhibits poor MyoD binding in RD cells, whereas JDP2 exhibits local DNA hypermethylation in its promoter in both RD cells and primary tumor samples. These results demonstrate that regional and local silencing of differentiation factors contributes to the differentiation defect in Rhabdomyosarcomas.
Jean Y. J. Wang - One of the best experts on this subject based on the ideXlab platform.
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association of ataxia telangiectasia mutated atm gene mutation deletion with Rhabdomyosarcoma
Molecular Cancer, 2003Co-Authors: Peilin Zhang, Kunjan S Bhakta, James R Feramisco, Robert O Newbury, Pier Lorenzo Puri, Jean Y. J. WangAbstract:Background Rhabdomyosarcoma is a common malignancy in children. There are two major types of Rhabdomyosarcomas, the embryonal and the alveolar, differing in cytogenetic and morphologic features. The alveolar type of Rhabdomyosarcoma is frequently associated with chromosome translocation t(2, 13) and poor clinical prognosis. Pathogenesis of Rhabdomyosarcoma remains obscure, and especially it occurs in the location where skeletal muscle is absent. We report here that there is a high frequency of association of Rhabdomyosarcoma with ataxia telangiectasia mutated (ATM) gene mutation/deletion.
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Association of Ataxia Telangiectasia Mutated (ATM) gene mutation/deletion with Rhabdomyosarcoma
Molecular Cancer, 2003Co-Authors: Peilin Zhang, Kunjan S Bhakta, James R Feramisco, Robert O Newbury, Pier Lorenzo Puri, Jean Y. J. WangAbstract:Background Rhabdomyosarcoma is a common malignancy in children. There are two major types of Rhabdomyosarcomas, the embryonal and the alveolar, differing in cytogenetic and morphologic features. The alveolar type of Rhabdomyosarcoma is frequently associated with chromosome translocation t(2, 13) and poor clinical prognosis. Pathogenesis of Rhabdomyosarcoma remains obscure, and especially it occurs in the location where skeletal muscle is absent. We report here that there is a high frequency of association of Rhabdomyosarcoma with ataxia telangiectasia mutated (ATM) gene mutation/deletion.
Nicholas D Socci - One of the best experts on this subject based on the ideXlab platform.
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A recurrent neomorphic mutation in MYOD1 defines a clinically aggressive subset of embryonal Rhabdomyosarcoma associated with PI3K-AKT pathway mutations
Nature Genetics, 2014Co-Authors: Shinji Kohsaka, Neerav Shukla, Nabahet Ameur, Tatsuo Ito, Lu Wang, Diana Lim, Angela Marchetti, Agnes Viale, Mono Pirun, Nicholas D SocciAbstract:Rhabdomyosarcoma, a cancer of skeletal muscle lineage, is the most common soft-tissue sarcoma in children^ 1 . Major subtypes of Rhabdomyosarcoma include alveolar (ARMS) and embryonal (ERMS) tumors^ 2 , 3 . Whereas ARMS tumors typically contain translocations generating PAX3 - FOXO1 or PAX7 - FOXO1 fusions that block terminal myogenic differentiation^ 4 , 5 , 6 , no functionally comparable genetic event has been found in ERMS tumors. Here we report the discovery, through whole-exome sequencing, of a recurrent somatic mutation encoding p.Leu122Arg in the myogenic transcription factor MYOD1 in a distinct subset of ERMS tumors with poor outcomes that also often contain mutations altering PI3K-AKT pathway components. Previous mutagenesis studies had shown that MYOD1 with a p.Leu122Arg substitution can block wild-type MYOD1 function and bind to MYC consensus sequences^ 7 , suggesting a possible switch from differentiation to proliferation. Our functional data now confirm this prediction. Thus, MYOD1 p.Leu122Arg defines a subset of Rhabdomyosarcomas eligible for high-risk protocols and the development of targeted therapeutics. Marc Ladanyi and colleagues identify a recurrent somatic mutation in MYOD1 in a subset of Rhabdomyosarcomas with poor outcome. The mutation alters the DNA binding and transactivation properties of MYOD1 and promotes a switch from differentiation to proliferation.
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a recurrent neomorphic mutation in myod1 defines a clinically aggressive subset of embryonal Rhabdomyosarcoma associated with pi3k akt pathway mutations
Nature Genetics, 2014Co-Authors: Shinji Kohsaka, Neerav Shukla, Nabahet Ameur, Tatsuo Ito, Lu Wang, Diana Lim, Angela Marchetti, Agnes Viale, Mono Pirun, Nicholas D SocciAbstract:Rhabdomyosarcoma, a cancer of skeletal muscle lineage, is the most common soft-tissue sarcoma in children. Major subtypes of Rhabdomyosarcoma include alveolar (ARMS) and embryonal (ERMS) tumors. Whereas ARMS tumors typically contain translocations generating PAX3-FOXO1 or PAX7-FOXO1 fusions that block terminal myogenic differentiation, no functionally comparable genetic event has been found in ERMS tumors. Here we report the discovery, through whole-exome sequencing, of a recurrent somatic mutation encoding p.Leu122Arg in the myogenic transcription factor MYOD1 in a distinct subset of ERMS tumors with poor outcomes that also often contain mutations altering PI3K-AKT pathway components. Previous mutagenesis studies had shown that MYOD1 with a p.Leu122Arg substitution can block wild-type MYOD1 function and bind to MYC consensus sequences, suggesting a possible switch from differentiation to proliferation. Our functional data now confirm this prediction. Thus, MYOD1 p.Leu122Arg defines a subset of Rhabdomyosarcomas eligible for high-risk protocols and the development of targeted therapeutics.
