MYCN-non-amplified metastatic neuroblastoma with good prognosis and spontaneous regression: A molecular portrait of stage 4S
MYCN-non-amplified metastatic neuroblastoma with good prognosis and spontaneous regression: A molecular portrait of stage 4S
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DOI：
10.1016/j.molonc.2008.07.002
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发表时间：
2008-10-01
影响因子：
6.6
通讯作者：
Valteau-Couanet, Dominique
中科院分区：
文献类型：
--
作者：
Benard, Jean;Raguenez, Gilda;Valteau-Couanet, Dominique
4期神经母细胞瘤（NB）在临床表现和行为上具有异质性。确实是婴儿（年龄365天的4S期和非4S期）。我们的研究旨在：(i)确定基于年龄的4期NB的基因组和基因表达谱，支持这种临床分层；（ii）寻找第4S阶段NB签名。使用1Mb BAC微阵列和Agilent 22K探针寡核苷酸微阵列对一组诊断时mycn -非扩增的4期NB肿瘤（n = 29例肿瘤，其中12例为4S期）进行差异基因组和转录组分析。过滤后的mRNA芯片数据在监督分层聚类之前产生信息基因，以识别肿瘤样本之间的关系。经定量RT-PCR确认后，获得一个4S期NB基因簇，并提交到验证集（n = 22个肿瘤）。婴儿肿瘤的基因组异常（整条染色体的增加或减少）与儿童肿瘤的基因组异常（染色体内重排）截然不同，但不能区分患有4S的婴儿和没有这种表现的婴儿。相比之下，通过观察个体基因和整个生物学途径的差异基因表达导致了分子阶段4S NB肖像，为这个迷人的实体提供了新的生物学线索。(C) 2008年欧洲生化学会联合会。Elsevier B.V.版权所有。
Stage 4 neuroblastoma (NB) are heterogeneous regarding their clinical presentations and behavior. Indeed infants (stage 4S and non-stage 4S of age 365 days). Our study aimed at: (i) identifying age-based genomic and gene expression profiles of stage 4 NB supporting this clinical stratification; and (ii) finding a stage 4S NB signature. Differential genome and transcriptome analyses of a learning set of MYCN-non amplified stage 4 NB tumors at diagnosis (n = 29 tumors including 12 stage 4S) were performed using 1Mb BAC microarrays and Agilent 22K probes oligo-microarrays. mRNA chips data following filtering yielded informative genes before supervised hierarchical clustering to identify relationship among tumor samples. After confirmation by quantitative RT-PCR, a stage 4S NB's gene cluster was obtained and submitted to a validation set (n = 22 tumors). Genomic abnormalities of infant's tumors (whole chromosomes gains or loss) differ radically from that of children (intra-chromosomal rearrangements) but could not discriminate infants with 4S from those without this presentation. In contrast, differential gene expression by looking at both individual genes and whole biological pathways leads to a molecular stage 4S NB portrait which provides new biological clues about this fascinating entity. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.