抑癌基因 FHIT 和 WWOX 在原发性渗出性淋巴瘤（PEL）细胞系中缺失。
Tumor suppressor genes FHIT and WWOX are deleted in primary effusion lymphoma (PEL) cell lines.
机构信息
Curriculum in Genetics and Molecular Biology, UNC Lineberger Comprehensive Cancer Center, UNC Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7290, USA.
出版信息
Blood. 2011 Aug 18;118(7):e32-9. doi: 10.1182/blood-2010-12-323659. Epub 2011 Jun 17.
Abstract
Primary effusion lymphoma (PEL) is a diffuse-large B-cell lymphoma with poor prognosis. One hundred percent of PELs carry the genome of Kaposi sarcoma-associated herpesvirus and a majority are coinfected with Epstein-Barr virus (EBV). We profiled genomic aberrations in PEL cells using the Affymetrix 6.0 SNP array. This identified for the first time individual genes that are altered in PEL cells. Eleven of 13 samples (85%) were deleted for the fragile site tumor suppressors WWOX and FHIT. Alterations were also observed in the DERL1, ETV1, RASA4, TPK1, TRIM56, and VPS41 genes, which are yet to be characterized for their roles in cancer. Coinfection with EBV was associated with significantly fewer gross genomic aberrations, and PEL could be segregated into EBV-positive and EBV-negative clusters on the basis of host chromosome alterations. This suggests a model in which both host genetic aberrations and the 2 viruses contribute to the PEL phenotype.
摘要
原发性渗出性淋巴瘤（PEL）是一种预后不良的弥漫性大 B 细胞淋巴瘤。100%的 PEL 携带卡波西肉瘤相关疱疹病毒的基因组，且大多数同时感染 Epstein-Barr 病毒（EBV）。我们使用 Affymetrix 6.0 SNP 芯片对 PEL 细胞中的基因组异常进行了分析。这是首次确定 PEL 细胞中发生改变的个别基因。13 个样本中的 11 个（85%）缺失脆性部位肿瘤抑制基因 WW0X 和 FHIT。在 DERL1、ETV1、RASA4、TPK1、TRIM56 和 VPS41 基因中也观察到了改变，这些基因在癌症中的作用尚待研究。与 EBV 共同感染与明显较少的总体基因组异常相关，并且可以根据宿主染色体改变将 PEL 分为 EBV 阳性和 EBV 阴性簇。这表明，宿主遗传异常和这两种病毒都促成了 PEL 表型。
相似文献
1
Tumor suppressor genes FHIT and WWOX are deleted in primary effusion lymphoma (PEL) cell lines.抑癌基因 FHIT 和 WWOX 在原发性渗出性淋巴瘤（PEL）细胞系中缺失。
Blood. 2011 Aug 18;118(7):e32-9. doi: 10.1182/blood-2010-12-323659. Epub 2011 Jun 17.
2
Expression of FRA16D/WWOX and FRA3B/FHIT genes in hematopoietic malignancies.FRA16D/WWOX和FRA3B/FHIT基因在血液系统恶性肿瘤中的表达
Mol Cancer Res. 2003 Nov;1(13):940-7.
3
Aberrant gene promoter methylation of p16, FHIT, CRBP1, WWOX, and DLC-1 in Epstein-Barr virus-associated gastric carcinomas.爱泼斯坦-巴尔病毒相关胃癌中p16、FHIT、CRBP1、WWOX和DLC-1基因启动子的异常甲基化
Med Oncol. 2015 Apr;32(4):92. doi: 10.1007/s12032-015-0525-y. Epub 2015 Feb 27.
4
Coordinate loss of fragile gene expression in pancreatobiliary cancers: correlations among markers and clinical features.胰胆管癌中脆弱基因表达的协同缺失：标志物与临床特征之间的相关性
Ann Surg Oncol. 2009 Aug;16(8):2331-8. doi: 10.1245/s10434-009-0507-4. Epub 2009 May 12.
5
A novel approach to simultaneously scan genes at fragile sites.一种同时扫描脆性位点基因的新方法。
BMC Cancer. 2006 Aug 8;6:205. doi: 10.1186/1471-2407-6-205.
6
Expression of fragile histidine triad (FHIT) and WW-domain oxidoreductase gene (WWOX) in nasopharyngeal carcinoma.脆性组氨酸三联体（FHIT）和WW结构域氧化还原酶基因（WWOX）在鼻咽癌中的表达
Asian Pac J Cancer Prev. 2013;14(1):165-71. doi: 10.7314/apjcp.2013.14.1.165.
7
Effect of exogenous E2F-1 on the expression of common chromosome fragile site genes, FHIT and WWOX.外源性E2F-1对常见染色体脆性位点基因FHIT和WWOX表达的影响。
Biochem Biophys Res Commun. 2004 Apr 16;316(4):1088-93. doi: 10.1016/j.bbrc.2004.02.159.
8
Epstein-Barr virus enhances genome maintenance of Kaposi sarcoma-associated herpesvirus.爱泼斯坦-巴尔病毒增强卡波西肉瘤相关疱疹病毒的基因组维持。
Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):E11379-E11387. doi: 10.1073/pnas.1810128115. Epub 2018 Nov 14.
9
Fhit and Wwox loss-associated genome instability: A genome caretaker one-two punch.Fhit和Wwox缺失相关的基因组不稳定：基因组守护者的双重打击。
Adv Biol Regul. 2017 Jan;63:167-176. doi: 10.1016/j.jbior.2016.09.008. Epub 2016 Sep 26.
10
Fragile histidine triad protein, WW domain-containing oxidoreductase protein Wwox, and activator protein 2gamma expression levels correlate with basal phenotype in breast cancer.脆性组氨酸三联体蛋白、含WW结构域的氧化还原酶蛋白Wwox和激活蛋白2γ的表达水平与乳腺癌的基础表型相关。
Cancer. 2009 Feb 15;115(4):899-908. doi: 10.1002/cncr.24103.
引用本文的文献
1
DNA methylation in monozygotic twins discordant for acute lymphoblastic leukemia: a case report and systematic review.急性淋巴细胞白血病不一致的同卵双胞胎中的DNA甲基化：一例报告及系统评价
Clin Epigenetics. 2025 Jun 6;17(1):94. doi: 10.1186/s13148-025-01906-z.
2
Mouse models of Kaposi sarcoma-associated herpesvirus (KSHV).卡波西肉瘤相关疱疹病毒（KSHV）的小鼠模型。
Virology. 2025 Feb;603:110384. doi: 10.1016/j.virol.2024.110384. Epub 2024 Dec 31.
3
Today's Kaposi sarcoma is not the same as it was 40 years ago, or is it?如今的卡波西肉瘤与 40 年前已大不相同，不是吗？
J Med Virol. 2023 May;95(5):e28773. doi: 10.1002/jmv.28773.
4
The Functions of TRIM56 in Antiviral Innate Immunity and Tumorigenesis.TRIM56 在抗病毒先天免疫和肿瘤发生中的功能。
Int J Mol Sci. 2023 Mar 6;24(5):5046. doi: 10.3390/ijms24055046.
5
Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response.全基因组关联研究与吸烟对结直肠癌风险的影响鉴定出与肿瘤抑制、炎症和免疫反应相关的新遗传位点。
Cancer Epidemiol Biomarkers Prev. 2023 Mar 6;32(3):315-328. doi: 10.1158/1055-9965.EPI-22-0763.
6
TRIM56 promotes malignant progression of glioblastoma by stabilizing cIAP1 protein.TRIM56 通过稳定 cIAP1 蛋白促进胶质母细胞瘤的恶性进展。
J Exp Clin Cancer Res. 2022 Dec 6;41(1):336. doi: 10.1186/s13046-022-02534-8.
7
Lymphoma-associated mutations in autoreactive memory B cells of patients with Sjögren's syndrome.干燥综合征患者自身反应性记忆 B 细胞中的淋巴瘤相关突变。
J Pathol. 2023 Mar;259(3):264-275. doi: 10.1002/path.6039. Epub 2023 Jan 12.
8
Expression Ratios of the Antiapoptotic BCL2 Family Members Dictate the Selective Addiction of Kaposi's Sarcoma-Associated Herpesvirus-Transformed Primary Effusion Lymphoma Cell Lines to MCL1.抗凋亡 BCL2 家族成员的表达比率决定了卡波氏肉瘤相关疱疹病毒转化的原发性渗出性淋巴瘤细胞系对 MCL1 的选择性成瘾。
J Virol. 2022 Dec 14;96(23):e0136022. doi: 10.1128/jvi.01360-22. Epub 2022 Nov 23.
9
Druggable host gene dependencies in primary effusion lymphoma.原发性渗出性淋巴瘤中可药物治疗的宿主基因依赖性。
Curr Opin Virol. 2022 Oct;56:101270. doi: 10.1016/j.coviro.2022.101270. Epub 2022 Sep 28.
10
The genomic and transcriptional landscape of primary central nervous system lymphoma.原发性中枢神经系统淋巴瘤的基因组和转录组图谱。
Nat Commun. 2022 May 10;13(1):2558. doi: 10.1038/s41467-022-30050-y.
本文引用的文献
1
Detection of genomic aberrations in molecularly defined Burkitt's lymphoma by array-based, high resolution, single nucleotide polymorphism analysis.通过基于阵列的、高分辨率的单核苷酸多态性分析检测分子定义的伯基特淋巴瘤中的基因组异常。
Haematologica. 2010 Dec;95(12):2047-55. doi: 10.3324/haematol.2010.026831. Epub 2010 Sep 7.
2
Recurrent chromosomal alterations in molecularly classified AIDS-related lymphomas: an integrated analysis of DNA copy number and gene expression.在分子分类的艾滋病相关淋巴瘤中反复出现的染色体改变：DNA 拷贝数和基因表达的综合分析。
J Acquir Immune Defic Syndr. 2010 May 1;54(1):18-26. doi: 10.1097/QAI.0b013e3181d3d9eb.
3
Molecular characterisation of ERG, ETV1 and PTEN gene loci identifies patients at low and high risk of death from prostate cancer.对 ERG、ETV1 和 PTEN 基因座的分子特征分析可识别前列腺癌死亡风险低和高的患者。
Br J Cancer. 2010 Feb 16;102(4):678-84. doi: 10.1038/sj.bjc.6605554. Epub 2010 Jan 26.
4
Accurate and objective copy number profiling using real-time quantitative PCR.使用实时定量 PCR 进行准确客观的拷贝数分析。
Methods. 2010 Apr;50(4):262-70. doi: 10.1016/j.ymeth.2009.12.007. Epub 2010 Jan 6.
5
High resolution genome-wide analysis of chromosomal alterations in Burkitt's lymphoma.高分辨率全基因组分析伯基特淋巴瘤的染色体改变。
PLoS One. 2009 Sep 17;4(9):e7089. doi: 10.1371/journal.pone.0007089.
6
Modulation of B-cell endoplasmic reticulum calcium homeostasis by Epstein-Barr virus latent membrane protein-1.EBV 潜伏膜蛋白 1 对 B 细胞内质网钙离子稳态的调节。
Mol Cancer. 2009 Aug 3;8:59. doi: 10.1186/1476-4598-8-59.
7
Mutational analysis of TP53, PTEN, PIK3CA and CTNNB1/beta-catenin genes in human herpesvirus 8-associated primary effusion lymphoma.人疱疹病毒8相关原发性渗出性淋巴瘤中TP53、PTEN、PIK3CA和CTNNB1/β-连环蛋白基因的突变分析
Haematologica. 2009 Aug;94(8):1170-4. doi: 10.3324/haematol.2009.007260. Epub 2009 Jul 16.
8
HIV-associated lymphomas and gamma-herpesviruses.人类免疫缺陷病毒相关淋巴瘤与γ-疱疹病毒
Blood. 2009 Feb 5;113(6):1213-24. doi: 10.1182/blood-2008-09-180315. Epub 2008 Oct 27.
9
EBV is necessary for proliferation of dually infected primary effusion lymphoma cells.EB病毒对于双重感染的原发性渗出性淋巴瘤细胞的增殖是必需的。
Cancer Res. 2008 Sep 1;68(17):6963-8. doi: 10.1158/0008-5472.CAN-08-0627.
10
Derlin-1 is overexpressed in human breast carcinoma and protects cancer cells from endoplasmic reticulum stress-induced apoptosis.Derlin-1在人类乳腺癌中过表达，并保护癌细胞免受内质网应激诱导的凋亡。
Breast Cancer Res. 2008;10(1):R7. doi: 10.1186/bcr1849. Epub 2008 Jan 20.
Zotero 插件