Genome wide DNA-profiling of HIV-related B-cell lymphomas.

Genome wide DNA-profiling of HIV-related B-cell lymphomas.
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DOI:
10.1111/j.1365-2141.2009.07943.x
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发表时间:
2010-01
影响因子:
6.5
通讯作者:
Bertoni F
Bertoni F
中科院分区:
医学2区
文献类型:
--
作者:
Capello D;Scandurra M;Poretti G;Rancoita PM;Mian M;Gloghini A;Deambrogi C;Martini M;Rossi D;Greiner TC;Chan WC;Ponzoni M;Moreno SM;Piris MA;Canzonieri V;Spina M;Tirelli U;Inghirami G;Rinaldi A;Zucca E;Favera RD;Cavalli F;Larocca LM;Kwee I;Carbone A;Gaidano G;Bertoni F

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非霍奇金淋巴瘤(NHL)是人类免疫缺陷病毒(HIV)感染的常见并发症。为了阐明HIV-NHL的发病机制,我们对57例HIV淋巴瘤和105例免疫活性弥漫性大B细胞淋巴瘤(IC-DLBCL)进行了基于单核苷酸多态性的微阵列比较基因组杂交的全基因组DNA图谱分析。基因组的复杂性因HIV-NHL亚型而异。HIV-Burkitt淋巴瘤的病变数目明显低于HIV-DLBCL(p=0.032),而EB病毒阴性的HIV-DLBCL的拷贝数变化的中位数(42.5%,8-153%)显著高于EBV-−阳性的病例(22例;3-41例;p=0.029)。与IC-DLBCL相比,HIV-DLBCL表现出独特的基因组图谱,没有18q的扩增,并有特异的遗传损伤。脆性位点相关基因,包括FHIT(FRA3B)、WWOX(FRA16D)、DCC(FRA18B)和PARK2(FRA6E)在HIV-NHL中经常因组织间隙缺失而失活,并且HIV-DLBCL中FHIT改变的发生率显著高于IC-DLBCL。脆性位点缺失所涉及的相同基因也经常受到调节区异常甲基化的影响。
Non-Hodgkin lymphomas (NHL) represent a frequent complication of human immunodeficiency virus (HIV) infection. To elucidate HIV-NHL pathogenesis, we performed a genome-wide DNA profiling based on a single nucleotide polymorphism-based microarray comparative genomic hybridization in 57 HIV-lymphomas and, for comparison, in 105 immunocompetent diffuse large B-cell lymphomas (IC-DLBCL). Genomic complexity varied across HIV-NHL subtypes. HIV-Burkitt lymphoma showed a significantly lower number of lesions than HIV-DLBCL (p=0.032), whereas the median number of copy number changes was significantly higher in Epstein-Barr virus negative (EBV−) HIV-DLBCL (42.5, range 8-153) compared to EBV+ cases (22; range 3-41; p=0.029). Compared to IC-DLBCL, HIV-DLBCL displayed a distinct genomic profile with no gains of 18q and specific genetic lesions. Fragile sites-associated genes, including FHIT (FRA3B), WWOX (FRA16D), DCC (FRA18B) and PARK2 (FRA6E) were frequently inactivated in HIV-NHL by interstitial deletions, and a significantly higher prevalence of FHIT alterations was observed in HIV-DLBCL compared to IC-DLBCL. The same genes involved by fragile site deletions were also frequently affected by aberrant methylation of regulative regions.
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