Genomic Amplifications and Distal 6q Loss: Novel Markers for Poor Survival in High-risk Neuroblastoma Patients.
Genomic Amplifications and Distal 6q Loss: Novel Markers for Poor Survival in High-risk Neuroblastoma Patients.
复制标题
DOI：
10.1093/jnci/djy022
复制
发表时间：
2018-10-01
期刊：
影响因子：
--
通讯作者：
De Preter K
中科院分区：
文献类型：
--
作者：
Depuydt P;Boeva V;Hocking TD;Cannoodt R;Ambros IM;Ambros PF;Asgharzadeh S;Attiyeh EF;Combaret V;Defferrari R;Fischer M;Hero B;Hogarty MD;Irwin MS;Koster J;Kreissman S;Ladenstein R;Lapouble E;Laureys G;London WB;Mazzocco K;Nakagawara A;Noguera R;Ohira M;Park JR;Pötschger U;Theissen J;Tonini GP;Valteau-Couanet D;Varesio L;Versteeg R;Speleman F;Maris JM;Schleiermacher G;De Preter K
神经母细胞瘤的特点是大量的临床异质性。尽管进行了强化治疗，高危神经母细胞瘤患者的存活率仍然低得令人不安。体细胞染色体拷贝数异常已被证明与患者的预后相关，特别是在低风险和中等风险的神经母细胞瘤患者中。为了提高对高危神经母细胞瘤预后的预测，我们设计了一种基于拷贝数畸变的预后分类方法。在一项国际合作中，从9个合作组收集了诊断时获得的556例高危神经母细胞瘤的标准化高分辨率DNA拷贝数数据（阵列CGH和SNP阵列），并使用相同的方法进行分割。我们应用逻辑回归和考克斯比例风险回归来确定与不良预后相关的基因组畸变。在这项研究中，我们确定了两种类型的拷贝数畸变与极差的结果。在5.9%的患者中检测到远端6q缺失，其10年生存概率仅为3.4%（95%置信区间[CI] = 0.5%至23.3%，双侧P = 0.002）。在18.1%的患者中检测到不包含MYCN基因座的区域扩增，其10年生存概率仅为5.8%（95% CI = 1.5%至22.2%，双侧P <0.001）。使用高风险神经母细胞瘤病例的独特大拷贝数数据集，我们确定了一小部分生存概率极低的高风险神经母细胞瘤患者，这些患者可能有资格纳入新疗法的临床试验。扩增子还可以指定靶向扩增基因的替代治疗。
Neuroblastoma is characterized by substantial clinical heterogeneity. Despite intensive treatment, the survival rates of high-risk neuroblastoma patients are still disappointingly low. Somatic chromosomal copy number aberrations have been shown to be associated with patient outcome, particularly in low- and intermediate-risk neuroblastoma patients. To improve outcome prediction in high-risk neuroblastoma, we aimed to design a prognostic classification method based on copy number aberrations. In an international collaboration, normalized high-resolution DNA copy number data (arrayCGH and SNP arrays) from 556 high-risk neuroblastomas obtained at diagnosis were collected from nine collaborative groups and segmented using the same method. We applied logistic and Cox proportional hazard regression to identify genomic aberrations associated with poor outcome. In this study, we identified two types of copy number aberrations that are associated with extremely poor outcome. Distal 6q losses were detected in 5.9% of patients and were associated with a 10-year survival probability of only 3.4% (95% confidence interval [CI] = 0.5% to 23.3%, two-sided P = .002). Amplifications of regions not encompassing the MYCN locus were detected in 18.1% of patients and were associated with a 10-year survival probability of only 5.8% (95% CI = 1.5% to 22.2%, two-sided P < .001). Using a unique large copy number data set of high-risk neuroblastoma cases, we identified a small subset of high-risk neuroblastoma patients with extremely low survival probability that might be eligible for inclusion in clinical trials of new therapeutics. The amplicons may also nominate alternative treatments that target the amplified genes.
登录
查看更多内容
复发的神经母细胞瘤显示出频繁的RAS-MAPK途径突变。
影响因子：
30.8
作者：
Eleveld TF;Oldridge DA;Bernard V;Koster J;Colmet Daage L;Diskin SJ;Schild L;Bentahar NB;Bellini A;Chicard M;Lapouble E;Combaret V;Legoix-Né P;Michon J;Pugh TJ;Hart LS;Rader J;Attiyeh EF;Wei JS;Zhang S;Naranjo A;Gastier-Foster JM;Hogarty MD;Asgharzadeh S;Smith MA;Guidry Auvil JM;Watkins TB;Zwijnenburg DA;Ebus ME;van Sluis P;Hakkert A;van Wezel E;van der Schoot CE;Westerhout EM;Schulte JH;Tytgat GA;Dolman ME;Janoueix-Lerosey I;Gerhard DS;Caron HN;Delattre O;Khan J;Versteeg R;Schleiermacher G;Molenaar JJ;Maris JM
通讯作者：
Maris JM
MDM2/X 靶向治疗的临床概述。
影响因子：
4.7
作者：
Burgess A;Chia KM;Haupt S;Thomas D;Haupt Y;Lim E
通讯作者：
Lim E
影响因子：
11.1
作者：
Ross-Adams H;Lamb AD;Dunning MJ;Halim S;Lindberg J;Massie CM;Egevad LA;Russell R;Ramos-Montoya A;Vowler SL;Sharma NL;Kay J;Whitaker H;Clark J;Hurst R;Gnanapragasam VJ;Shah NC;Warren AY;Cooper CS;Lynch AG;Stark R;Mills IG;Grönberg H;Neal DE;CamCaP Study Group
通讯作者：
CamCaP Study Group
影响因子：
6.4
作者：
Coco, Simona;Theissen, Jessica;Tonini, Gian Paolo
通讯作者：
Tonini, Gian Paolo
影响因子：
5.2
作者：
Peddibhotla, Sirisha;Nagamani, Sandesh C. S.;Cheung, Sau W.
通讯作者：
Cheung, Sau W.