1号染色体短臂和11号染色体长臂缺失与神经母细胞瘤的预后

Chromosome 1p and 11q deletions and outcome in neuroblastoma.

作者信息

Attiyeh Edward F, London Wendy B, Mossé Yael P, Wang Qun, Winter Cynthia, Khazi Deepa, McGrady Patrick W, Seeger Robert C, Look A Thomas, Shimada Hiroyuki, Brodeur Garrett M, Cohn Susan L, Matthay Katherine K, Maris John M

机构信息

Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, PA 19104-4318, USA.

出版信息

N Engl J Med. 2005 Nov 24;353(21):2243-53. doi: 10.1056/NEJMoa052399.

DOI:10.1056/NEJMoa052399

PMID:16306521

Abstract

BACKGROUND

Neuroblastoma is a childhood cancer with considerable morbidity and mortality. Tumor-derived biomarkers may improve risk stratification.

METHODS

We screened 915 samples of neuroblastoma for loss of heterozygosity (LOH) at chromosome bands 1p36 and 11q23. Additional analyses identified a subgroup of cases of 11q23 LOH with unbalanced 11q LOH (unb11q LOH; defined as loss of 11q with retention of 11p). The associations of LOH with relapse and survival were determined.

RESULTS

LOH at 1p36 was identified in 209 of 898 tumors (23 percent) and LOH at 11q23 in 307 of 913 (34 percent). Unb11q LOH was found in 151 of 307 tumors with 11q23 LOH (17 percent of the total cohort). There was a strong association of 1p36 LOH, 11q23 LOH, and unb11q LOH with most high-risk disease features (P<0.001). LOH at 1p36 was associated with amplification of the MYCN oncogene (P<0.001), but 11q23 LOH and unb11q LOH were not (P<0.001 and P=0.002, respectively). Cases with unb11q LOH were associated with three-year event-free and overall survival rates (+/-SE) of 50+/-5 percent and 66+/-5 percent, respectively, as compared with 74+/-2 percent and 83+/-2 percent among cases without unb11q LOH (P<0.001 for both comparisons). In a multivariate model, unb11q LOH was independently associated with decreased event-free survival (P=0.009) in the entire cohort, and both 1p36 LOH and unb11q LOH were independently associated with decreased progression-free survival in the subgroup of patients with features of low-risk and intermediate-risk disease (P=0.002 and P=0.02, respectively).

CONCLUSIONS

Unb11q LOH and 1p36 LOH are independently associated with a worse outcome in patients with neuroblastoma.

摘要

背景

神经母细胞瘤是一种儿童期癌症，具有较高的发病率和死亡率。肿瘤衍生的生物标志物可能会改善风险分层。

方法

我们对915份神经母细胞瘤样本进行筛查，以检测1p36和11q23染色体带的杂合性缺失（LOH）。进一步分析确定了一组11q23 LOH且伴有不平衡11q LOH（unb11q LOH；定义为11q缺失而11p保留）的病例亚组。确定了LOH与复发和生存的关联。

结果

在898个肿瘤中的209个（23%）中检测到1p36 LOH，在913个中的307个（34%）中检测到11q23 LOH。在307个有11q23 LOH的肿瘤中有151个发现unb11q LOH（占整个队列的17%）。1p36 LOH、11q23 LOH和unb11q LOH与大多数高危疾病特征密切相关（P<0.001）。1p36 LOH与MYCN癌基因扩增相关（P<0.001），但11q23 LOH和unb11q LOH则不然（分别为P<0.001和P=0.002）。有unb11q LOH的病例的三年无事件生存率和总生存率（±SE）分别为50±5%和66±5%，而无unb11q LOH的病例分别为74±2%和83±2%（两项比较P均<0.001）。在多变量模型中，unb11q LOH在整个队列中与无事件生存率降低独立相关（P=0.009），在具有低危和中危疾病特征的患者亚组中，1p36 LOH和unb11q LOH均与无进展生存率降低独立相关（分别为P=0.002和P=0.02）。