Array-based comparative genomic hybridization analysis reveals chromosomal copy number aberrations associated with clinical outcome in canine diffuse large B-cell lymphoma.
Array-based comparative genomic hybridization analysis reveals chromosomal copy number aberrations associated with clinical outcome in canine diffuse large B-cell lymphoma.
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DOI：
10.1371/journal.pone.0111817
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Aresu L
中科院分区：
文献类型：
--
作者：
Aricò A;Ferraresso S;Bresolin S;Marconato L;Comazzi S;Te Kronnie G;Aresu L
犬弥漫性大B细胞淋巴瘤（cDLBCL）是一种侵袭性癌症，临床反应多变。尽管最近尝试通过基因表达谱来鉴定狗作为人DLBCL的潜在动物模型，但这种肿瘤仍然具有生物学异质性，没有预后生物标志物来预测预后。本工作的目的是确定拷贝数畸变（CNA）的高分辨率阵列比较基因组杂交（aCGH）在12只狗与新诊断的DLBCL。在这些犬的一个亚组中，还评估了治疗结束时和复发时的遗传特征。在原发性DLBCL中，计数了90种不同的基因组不平衡，包括46种增益和44种损失。chr13的两个增加与临床分期显著相关。此外，特定区域的收益和损失显着相关的缓解持续时间。在原发性DLBCL中，发现了个体差异，但确定了14例复发性CNA（>30%）。总是发现涉及IGK、IGL和IGH的损失，并且经常观察到沿着chr13和chr31长度的增益（>41%）。在这些片段中，注释了MYC、LDHB、HSF 1、KIT和PDGFRα。在治疗结束时，缓解犬显示出4个新的CNA，而与之前的特征相比，复发犬中观察到3个新的CNA。治疗后缓解的犬中存在一例涉及TCR的新发CNA，可能由自体疫苗诱导。总体而言，aCGH鉴定了与结果相关的小CNA，沿着未来的表达研究，可能揭示与cDLBCL相关的靶基因。
Canine Diffuse Large B-cell Lymphoma (cDLBCL) is an aggressive cancer with variable clinical response. Despite recent attempts by gene expression profiling to identify the dog as a potential animal model for human DLBCL, this tumor remains biologically heterogeneous with no prognostic biomarkers to predict prognosis. The aim of this work was to identify copy number aberrations (CNAs) by high-resolution array comparative genomic hybridization (aCGH) in 12 dogs with newly diagnosed DLBCL. In a subset of these dogs, the genetic profiles at the end of therapy and at relapse were also assessed. In primary DLBCLs, 90 different genomic imbalances were counted, consisting of 46 gains and 44 losses. Two gains in chr13 were significantly correlated with clinical stage. In addition, specific regions of gains and losses were significantly associated to duration of remission. In primary DLBCLs, individual variability was found, however 14 recurrent CNAs (>30%) were identified. Losses involving IGK, IGL and IGH were always found, and gains along the length of chr13 and chr31 were often observed (>41%). In these segments, MYC, LDHB, HSF1, KIT and PDGFRα are annotated. At the end of therapy, dogs in remission showed four new CNAs, whereas three new CNAs were observed in dogs at relapse compared with the previous profiles. One ex novo CNA, involving TCR, was present in dogs in remission after therapy, possibly induced by the autologous vaccine. Overall, aCGH identified small CNAs associated with outcome, which, along with future expression studies, may reveal target genes relevant to cDLBCL.
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影响因子：
3.2
作者：
BAUER, TR;MCDERMID, HE;BLOMBERG, BB
通讯作者：
BLOMBERG, BB
影响因子：
64.8
作者：
Greaves, Mel;Maley, Carlo C.
通讯作者：
Maley, Carlo C.
影响因子：
2.1
作者：
Aresu, L.;Martini, V.;Marconato, L.
通讯作者：
Marconato, L.
影响因子：
3.3
作者：
Capello, Daniela;Cerri, Michaela;Gaidano, Gianluca
通讯作者：
Gaidano, Gianluca
DOI：
10.1186/1756-9966-31-100
发表时间：
2012-11-30
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Kanamori M;Sano A;Yasuda T;Hori T;Suzuki K
通讯作者：
Suzuki K