Genome-wide analysis of neuroblastomas using high-density single nucleotide polymorphism arrays.
Genome-wide analysis of neuroblastomas using high-density single nucleotide polymorphism arrays.
复制标题
DOI：
10.1371/journal.pone.0000255
复制
发表时间：
2007-02-28
期刊：
影响因子：
3.7
通讯作者：
Maris JM
中科院分区：
文献类型：
--
作者：
George RE;Attiyeh EF;Li S;Moreau LA;Neuberg D;Li C;Fox EA;Meyerson M;Diller L;Fortina P;Look AT;Maris JM
神经母细胞瘤的特征是染色体改变，具有生物学和临床意义。我们使用Affyss 10 K单核苷酸多态性（SNP）阵列分析了22例高危神经母细胞瘤患儿的配对血液和原发肿瘤样本的杂合性丢失（洛）和DNA拷贝数变化。观察到多个区域的洛缺失和拷贝数增加。最常见的洛缺失区域位于染色体臂11 q（15/22; 68%）。染色体11 q洛与染色体3 p洛的发生高度相关：15例11 q洛中有9例同时存在3 p洛（P = 0.016）。 三分之一的病例可见染色体1 p洛缺失。染色体11 q和1 p上的洛缺失事件通常伴随着拷贝数的丢失，表明这些区域内存在半合子缺失。一个例外是在染色体11 p上，在所有四个病例中的洛缺失都伴随着正常的拷贝数或二倍体，这意味着单亲二体性。拷贝数的增加最常在染色体臂17 q上观察到（21/22个样品; 95%），并且在6个样品中与等位基因不平衡相关。还观察到MYCN扩增，并且在单个病例中还观察到第二个基因ALK扩增。该分析证明了SNP阵列用于神经母细胞瘤中洛缺失和DNA拷贝数变化的高分辨率测定的能力，神经母细胞瘤是一种特定等位基因变化驱动临床结果和治疗选择的肿瘤。
Neuroblastomas are characterized by chromosomal alterations with biological and clinical significance. We analyzed paired blood and primary tumor samples from 22 children with high-risk neuroblastoma for loss of heterozygosity (LOH) and DNA copy number change using the Affymetrix 10K single nucleotide polymorphism (SNP) array. Multiple areas of LOH and copy number gain were seen. The most commonly observed area of LOH was on chromosome arm 11q (15/22 samples; 68%). Chromosome 11q LOH was highly associated with occurrence of chromosome 3p LOH: 9 of the 15 samples with 11q LOH had concomitant 3p LOH (P = 0.016). Chromosome 1p LOH was seen in one-third of cases. LOH events on chromosomes 11q and 1p were generally accompanied by copy number loss, indicating hemizygous deletion within these regions. The one exception was on chromosome 11p, where LOH in all four cases was accompanied by normal copy number or diploidy, implying uniparental disomy. Gain of copy number was most frequently observed on chromosome arm 17q (21/22 samples; 95%) and was associated with allelic imbalance in six samples. Amplification of MYCN was also noted, and also amplification of a second gene, ALK, in a single case. This analysis demonstrates the power of SNP arrays for high-resolution determination of LOH and DNA copy number change in neuroblastoma, a tumor in which specific allelic changes drive clinical outcome and selection of therapy.
登录
查看更多内容
影响因子：
6
作者：
Osajima-Hakomori, Y;Miyake, I;Sakai, R
通讯作者：
Sakai, R
影响因子：
45.3
作者：
BRODEUR, GM;PRITCHARD, J;VOUTE, PA
通讯作者：
VOUTE, PA
影响因子：
158.5
作者：
Bown, N;Cotterill, S;Speleman, F
通讯作者：
Speleman, F
影响因子：
158.5
作者：
SEEGER, RC;BRODEUR, GM;HAMMOND, D
通讯作者：
HAMMOND, D
影响因子：
4.8
作者：
Mathew, P;Valentine, MB;Look, AT
通讯作者：
Look, AT