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Hu, Xiaozhou; Baytak, Esra; Li, Jinnan; Akman, Burcu; Okay, Kaan; Hu, Genfu; Scuto, Anna; Zhang, Wenyan; Kucuk, Can
{ "@context": "https://schema.org/", "@id": 43897, "@type": "ScholarlyArticle", "creator": [ { "@type": "Person", "affiliation": "Dokuz Eylul Univ, Izmir Int Biomed & Genome Inst iBG Izmir, Izmir, Turkey", "name": "Hu, Xiaozhou" }, { "@type": "Person", "name": "Baytak, Esra" }, { "@type": "Person", "affiliation": "Sichuan Univ, West China Hosp, Dept Pathol, Chengdu, Guangxi, Peoples R China", "name": "Li, Jinnan" }, { "@type": "Person", "affiliation": "Dokuz Eylul Univ, Izmir Int Biomed & Genome Inst iBG Izmir, Izmir, Turkey", "name": "Akman, Burcu" }, { "@type": "Person", "affiliation": "Dokuz Eylul Univ, Izmir Int Biomed & Genome Inst iBG Izmir, Izmir, Turkey", "name": "Okay, Kaan" }, { "@type": "Person", "name": "Hu, Genfu" }, { "@type": "Person", "affiliation": "City Hope Med Ctr, Dept Pathol, Duarte, CA USA", "name": "Scuto, Anna" }, { "@type": "Person", "affiliation": "Sichuan Univ, West China Hosp, Dept Pathol, Chengdu, Guangxi, Peoples R China", "name": "Zhang, Wenyan" }, { "@type": "Person", "name": "Kucuk, Can" } ], "datePublished": "2017-01-01", "description": "Follicular lymphoma (FL) is a common type of indolent lymphoma that occasionally transforms to more aggressive B-cell lymphomas. These transformed follicular lymphomas (tFL) are often associated with chemoresistance whose mechanisms are currently unknown. REL, a proto-oncogene located on frequently amplified 2p16.1-p15 locus, promotes tumorigenesis in many cancer types through deregulation of the NF-KB pathway; however, its role in FL pathobiology or chemoresistance has not been addressed. Here, we evaluated REL gene copy number by q-PCR on FFPE FL tumor samples, and observed REL amplification in 30.4% of FL cases that was associated with weak elevation of transcript levels. PCR-Sanger analysis did not show any somatic mutation in FL tumors. In support of a marginal oncogenic role, a REL-transduced FL cell line was positively selected under limiting serum conditions. Interestingly, reanalysis of previously reported gene expression profiles revealed significant enrichment of DNA damage-induced repair and cell cycle arrest pathways in tFL tumors with high REL expression compared to those with low REL expression consistent with the critical role of c-REL in genotoxicity-induced NF-KB signaling, which was reported to lead to drug resistance. In addition to DNA damage repair genes such as ATM and BRCA1, anti-apoptotic BCL2 was significantly elevated in REL-high FL and tFL tumors. Altogether these data suggest that other genes located in amplified 2p16.1-p15 locus may have more oncogenic role in FL etiology; however, high REL expression may be useful as a predictive biomarker of response to immunochemotherapy, and inhibition of c-REL may potentially sensitize resistant FL or tFL cells to chemotherapy. (C) 2017 Elsevier Ltd. All rights reserved.", "headline": "The relationship of REL proto-oncogene to pathobiology and chemoresistance in follicular and transformed follicular lymphoma", "identifier": 43897, "image": "https://aperta.ulakbim.gov.tr/static/img/logo/aperta_logo_with_icon.svg", "license": "http://www.opendefinition.org/licenses/cc-by", "name": "The relationship of REL proto-oncogene to pathobiology and chemoresistance in follicular and transformed follicular lymphoma", "url": "https://aperta.ulakbim.gov.tr/record/43897" }
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