Specific gene expression profiles and chromosomal abnormalities are associated with infant disseminated neuroblastoma.

Specific gene expression profiles and chromosomal abnormalities are associated with infant disseminated neuroblastoma.
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DOI:
10.1186/1471-2407-9-44
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发表时间:
2009-02-03
期刊:
影响因子:
3.8
通讯作者:
Mora, Jaume
Mora, Jaume
中科院分区:
医学2区
文献类型:
--
作者:
Lavarino, Cinzia;Cheung, Nai-Kong V.;Garcia, Idoia;Domenech, Gema;de Torres, Carmen;Alaminos, Miguel;Rios, Jose;Gerald, William L.;Kushner, Brian;LaQuaglia, Mike;Mora, Jaume

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神经母细胞瘤(NB)肿瘤具有最高的自发缓解发生率,特别是在影响婴儿的4期NB亚组中。临床区分4期和致死性4期可能很困难,但对治疗决策至关重要。本研究的目的是研究婴儿弥散性NB亚群的染色体改变和差异基因表达。通过等位基因和基因表达分析对35例未满18个月确诊的NB肿瘤(25例4期和10例4期)进行评估。所有的4期患者均自发缓解,只有48%的4期患者在联合治疗后存活。4期肿瘤90%为近二倍体/四倍体,44% MYCN扩增,77%为1p LOH(50%为1p36), 23%为11q和/或14q LOH(27%), 47%为17q增益。第4期90%为近三倍体,没有MYCN扩增,LOH限制在11q。第4期和第4期< 12个月肿瘤的初步比较分析显示出不同的基因表达谱。大部分基因定位在1号染色体上(P < 0.0001), 90%的基因在第4期表达较高,11号染色体(P = 0.0054), 91%的基因在第4期表达较高。在第4期和第4期< 18m之间观察到的表达谱不太明确,但与1号染色体(P < 0.0001)和11号染色体(P = 0.005)的关联保持不变。在没有MYCN扩增的第4期和第4期< 18个月时,观察到不同的基因表达谱,但与特定染色体区域定位没有显著关联。特定的染色体畸变与不同的基因表达谱有关,这些基因表达谱是自发退化或侵袭性婴儿NB的特征,为不同的临床行为提供了生物学基础。
Neuroblastoma (NB) tumours have the highest incidence of spontaneous remission, especially among the stage 4s NB subgroup affecting infants. Clinical distinction of stage 4s from lethal stage 4 can be difficult, but critical for therapeutic decisions. The aim of this study was to investigate chromosomal alterations and differential gene expression amongst infant disseminated NB subgroups. Thirty-five NB tumours from patients diagnosed at < 18 months (25 stage 4 and 10 stage 4s), were evaluated by allelic and gene expression analyses. All stage 4s patients underwent spontaneous remission, only 48% stage 4 patients survived despite combined modality therapy. Stage 4 tumours were 90% near-diploid/tetraploid, 44% MYCN amplified, 77% had 1p LOH (50% 1p36), 23% 11q and/or 14q LOH (27%) and 47% had 17q gain. Stage 4s were 90% near-triploid, none MYCN amplified and LOH was restricted to 11q. Initial comparison analyses between stage 4s and 4 < 12 months tumours revealed distinct gene expression profiles. A significant portion of genes mapped to chromosome 1 (P < 0.0001), 90% with higher expression in stage 4s, and chromosome 11 (P = 0.0054), 91% with higher expression in stage 4. Less definite expression profiles were observed between stage 4s and 4 < 18m, yet, association with chromosomes 1 (P < 0.0001) and 11 (P = 0.005) was maintained. Distinct gene expression profiles but no significant association with specific chromosomal region localization was observed between stage 4s and stage 4 < 18 months without MYCN amplification. Specific chromosomal aberrations are associated with distinct gene expression profiles which characterize spontaneously regressing or aggressive infant NB, providing the biological basis for the distinct clinical behaviour.
DOI: 10.1023/a:1005778607661
发表时间: 1997-01-01
影响因子: 3.9
作者:
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发表时间: 1995-01-01
影响因子: 5.8
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DOI: 10.1038/sj.onc.1202887
发表时间: 1999-09-02
期刊: ONCOGENE
影响因子: 8
作者:
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