Differential expression of genes mapping to recurrently abnormal chromosomal regions characterize neuroblastic tumours with distinct ploidy status.
Differential expression of genes mapping to recurrently abnormal chromosomal regions characterize neuroblastic tumours with distinct ploidy status.
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DOI：
10.1186/1755-8794-1-36
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发表时间：
2008-08-13
影响因子：
2.7
通讯作者：
Mora J
中科院分区：
文献类型：
--
作者：
Lavarino C;Garcia I;Mackintosh C;Cheung NK;Domenech G;Ríos J;Perez N;Rodríguez E;de Torres C;Gerald WL;Tuset E;Acosta S;Beleta H;de Alava E;Mora J
神经母细胞瘤（NBT）代表了与多种遗传改变相关的肿瘤性疾病的异质谱。染色体结构和数量的变化是常见的，是NBT结果的预测参数。我们对不同倍性状态的NBT构成的生物实体进行了比较分析。使用寡核苷酸芯片对49例具有倍性数据的诊断性原发性NBT进行基因表达谱分析。采用定量实时聚合酶链反应（Q-PCR）、阵列比较基因组杂交（aCGH）和荧光原位杂交（FISH）进行进一步分析，以研究非整倍体、染色体变化和基因表达谱之间的相关性。49个主要的近三倍体和近二倍体/四倍体NBT的基因表达谱显示不同的表达谱与每个NBT亚组。统计学显著性部分基因定位于1 p36（P = 0.01）和17 p13-q21（P < 0.0001），描述为NBT中的复发性改变。这些基因中超过90%在近三倍体NBT中表现出较高的表达，并且大多数参与细胞分化途径。在NBT中观察到的特定染色体异常，1 p丢失，17 q和整个17号染色体获得，反映在基因表达谱中。基因拷贝数和表达水平之间的比较表明，差异表达可能只是部分依赖于基因拷贝数。在所有NBT中观察到肿瘤内克隆异质性，在近二倍体/四倍体肿瘤中具有显著的克隆间变异性。具有不同细胞DNA含量的NBT显示不同的转录谱，其中显著部分的差异表达基因定位到已知与结果相关的特定染色体区域。此外，我们的研究结果表明，这些特定的遗传异常是高度异质性在所有的NBT，并表明，NBT与不同的倍性状态可能会导致不同的非整倍体驱动肿瘤发生的机制。
Neuroblastic tumours (NBTs) represent a heterogeneous spectrum of neoplastic diseases associated with multiple genetic alterations. Structural and numerical chromosomal changes are frequent and are predictive parameters of NBTs outcome. We performed a comparative analysis of the biological entities constituted by NBTs with different ploidy status. Gene expression profiling of 49 diagnostic primary NBTs with ploidy data was performed using oligonucleotide microarray. Further analyses using Quantitative Real-Time Polymerase Chain Reaction (Q-PCR); array-Comparative Genomic Hybridization (aCGH); and Fluorescent in situ Hybridization (FISH) were performed to investigate the correlation between aneuploidy, chromosomal changes and gene expression profiles. Gene expression profiling of 49 primary near-triploid and near-diploid/tetraploid NBTs revealed distinct expression profiles associated with each NBT subgroup. A statistically significant portion of genes mapped to 1p36 (P = 0.01) and 17p13-q21 (P < 0.0001), described as recurrently altered in NBTs. Over 90% of these genes showed higher expression in near-triploid NBTs and the majority are involved in cell differentiation pathways. Specific chromosomal abnormalities observed in NBTs, 1p loss, 17q and whole chromosome 17 gains, were reflected in the gene expression profiles. Comparison between gene copy number and expression levels suggests that differential expression might be only partly dependent on gene copy number. Intratumoural clonal heterogeneity was observed in all NBTs, with marked interclonal variability in near-diploid/tetraploid tumours. NBTs with different cellular DNA content display distinct transcriptional profiles with a significant portion of differentially expressed genes mapping to specific chromosomal regions known to be associated with outcome. Furthermore, our results demonstrate that these specific genetic abnormalities are highly heterogeneous in all NBTs, and suggest that NBTs with different ploidy status may result from different mechanisms of aneuploidy driving tumourigenesis.
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DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
4.3
作者：
Janoueix-Lerosey, I;Hupé, P;Delattre, O
通讯作者：
Delattre, O
影响因子：
15.9
作者：
KEIM, D;HAILAT, N;HANASH, SM
通讯作者：
HANASH, SM
影响因子：
6.2
作者：
Mora, J;Gerald, WL;Cheung, NKV
通讯作者：
Cheung, NKV
影响因子：
56.9
作者：
BRODEUR, GM;SEEGER, RC;BISHOP, JM
通讯作者：
BISHOP, JM