High-risk neuroblastoma tumors with 11q-deletion display a poor prognostic, chromosome instability phenotype with later onset
High-risk neuroblastoma tumors with 11q-deletion display a poor prognostic, chromosome instability phenotype with later onset
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DOI：
10.1073/pnas.0910684107
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发表时间：
2010-03-02
影响因子：
11.1
通讯作者：
Martinsson, Tommy
中科院分区：
文献类型：
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作者：
Caren, Helena;Kryh, Hanna;Martinsson, Tommy
染色体畸变的分析用于确定神经母细胞瘤（NB）的预后和帮助治疗决策。仅MYCN扩增（MNA）是一个不完整的预后因素，而染色体11Q状态最近已包括在风险分类中。我们使用高密度SNP微阵列分析了165个NB肿瘤，并特别比较了由MNA（n = 37）和11Q- DELETION（n = 21）定义的高风险基团。 MNA肿瘤的诊断患者中位数为21个月，11Q-缺失肿瘤的患者年龄为42个月，诊断后的中位生存时间为16个月，MNA为16个月，11Q缺失为40个月。两组的总生存期（8年）与35％相似。 MNA和11Q缺失几乎是互斥的。只有一个案件都有两个畸变。节段畸变的数量差异很大。 MNA组的中位数为四个畸变，而11q删除组的中位数为12。11q-缺骨组中的高染色体断裂频率提示位于11Q的染色体不稳定性表型基因；一个这样的基因H2AFX位于11q23.3（在11q删除区域内）。此外，在没有MNA或11Q缺失的分段像差的组中，具有17q增益的肿瘤的预后较差，而没有17Q增益的分段畸变的肿瘤则具有优惠的结果。这项研究对不同风险群体的治疗具有影响，并强调应将全基因组微阵列分析纳入临床管理中，以充分评估风险，帮助诊断和指导治疗。
Analysis of chromosomal aberrations is used to determine the prognosis of neuroblastomas (NBs) and to aid treatment decisions. MYCN amplification (MNA) alone is an incomplete poor prognostic factor, and chromosome 11q status has recently been included in risk classification. We analyzed 165 NB tumors using high-density SNP microarrays and specifically compared the high-risk groups defined by MNA (n = 37) and 11q- deletion (n = 21). Median patient age at diagnosis was 21 months for MNA tumors and 42 months for 11q- deletion tumors, and median survival time after diagnosis was 16 months for MNA and 40 months for 11q deletion. Overall survival (at 8 years) was similar to 35% in both groups. MNA and 11q deletion were almost mutually exclusive; only one case harbored both aberrations. The numbers of segmental aberrations differed significantly; the MNA group had a median of four aberrations, whereas the 11q-deletion group had 12. The high frequency of chromosomal breaks in the 11q-deletion group is suggestive of a chromosomal instability phenotype gene located in 11q; one such gene, H2AFX, is located in 11q23.3 (within the 11q-deletion region). Furthermore, in the groups with segmental aberrations without MNA or 11q deletion, the tumors with 17q gain have worse prognosis than those with segmental aberrations without 17q gain, which have a favorable outcome. This study has implications for therapy in different risk groups and stresses that genome-wide microarray analyses should be included in clinical management to fully evaluate risk, aid diagnosis, and guide treatment.