Allelic deletion at 11q23 is common in MYCN single copy neuroblastomas
Allelic deletion at 11q23 is common in MYCN single copy neuroblastomas
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DOI：
10.1038/sj.onc.1202887
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发表时间：
1999-09-02
期刊：
影响因子：
8
通讯作者：
Maris, JM
中科院分区：
文献类型：
--
作者：
Guo, C;White, PS;Maris, JM
11号染色体长臂(11q)的缺失在原发神经母细胞瘤中已被发现，但尚未进行全面的分析。因此，我们分析了331个神经母细胞瘤(295个散发性的，15个家族性的和21个肿瘤来源的细胞系)，以确定11q等位基因缺失的发生率，定位一个可能的肿瘤抑制基因的位置，并进行临床相关研究。对分布于11q的24个微卫星座位进行杂合性缺失(LOH)检测，在129/295(44%)个散发性神经母细胞瘤、5/15(33%)家族性神经母细胞瘤和5/21(24%)神经母细胞瘤细胞系中检测到多个11q位点的杂合性缺失。在所有11q LOH的样本中，11q23，3内的一个2.1 cM的区域被D11S1340和D11S1299标记缺失，11q23的等位基因缺失与MYCN扩增呈负相关(P<；在MYCN单一拷贝的病例子集中，11q LOH与晚期疾病(P=0,008)、不良的组织病理学(P=0,042)和降低的总体生存概率(P=0,008)有关，然而，在多因素分析中，11q LOH并不是独立的预后因素，这些数据支持这样的假设，即11q23，3内的肿瘤抑制基因映射通常在大亚组神经母细胞瘤的恶变过程中失活，尤其是那些未扩增的MYCN。
Deletions of the long arm of chromosome 11 (11q) have been noted in primary neuroblastomas, but a comprehensive analysis has not been performed. Therefore, we analysed 331 neuroblastomas (295 sporadic, 15 familial and 21 tumor-derived cell Lines) to determine the prevalence of 11q allelic deletions, to map the location of a putative tumor suppressor gene and to perform clinical correlative studies. Assays for loss of heterozygosity (LOH) were performed at 24 microsatellite loci spanning 11q, LOH was observed at multiple 11q loci in 129/295 (44%) sporadic neuroblastomas, 5/15 (33%) familial neuroblastomas, and 5/21 (24%) neuroblastoma cell lines. A single region of 2.1 cM within 11q23,3, flanked by markers D11S1340 and D11S1299, was deleted in all specimens with 11q LOH, Allelic loss at 11q23 was inversely related to MYCN amplification (P < 0,001), Within the subset of cases with a single copy of MYCN 11q LOH was associated with advanced stage disease (P = 0,008), unfavorable histopathology (P = 0,042), and decreased overall survival probability (P = 0,008), However, 11q LOH was not independently prognostic in multivariate analyses, These data support the hypothesis that a tumor suppressor gene mapping within 11q23,3 is commonly inactivated during the malignant evolution of a large subset of neuroblastomas, especially those with unamplified MYCN.