神经母细胞瘤基因组结构性变异特征的研究进展

韩雷; 杨嘉兴; 龚宝成; 赵强

doi:10.12354/j.issn.1000-8179.2023.20221573

神经母细胞瘤基因组结构性变异特征的研究进展

doi: 10.12354/j.issn.1000-8179.2023.20221573

韩雷^1,,
杨嘉兴²,
龚宝成²,
赵强^2, ,

1.
天津医科大学肿瘤医院肿瘤分子诊断中心，国家恶性肿瘤临床医学研究中心，天津市"肿瘤防治"重点实验室，天津市恶性肿瘤临床医学研究中心（天津市300060）
2.
儿童肿瘤科

基金项目: 本文课题受国家科学技术部重大慢性非传染性疾病防控研究项目（编号：2018YFC1313000和2018YFC1313001）资助

详细信息

作者简介:
韩雷：专业方向为儿童肿瘤生物大数据分析

通讯作者:
赵强　zhaoqiang@tjmuch.com

计量
- 文章访问数: 47
- HTML全文浏览量: 7
- PDF下载量: 18
- 被引次数: 0
出版历程
- 收稿日期: 2022-11-07
- 录用日期: 2023-04-04
- 修回日期: 2023-04-03

Research progress on the characterization of structural variants in neuroblastoma genome

1.
Cancer Molecular Diagnostics Core
2.
Department of Pediatric Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China

Funds: This work was supported by the National Key Research and Development Program of China (No. 2018YFC13130000, No. 2018YFC13130001)

More Information

Corresponding author: Qiang Zhao; E-mail: zhaoqiang@tjmuch.com

摘要

摘要: 神经母细胞瘤（neuroblastoma，NB）是起源于神经嵴细胞的儿童胚胎恶性肿瘤，表现为较强的生物学和临床异质性。基因组测序研究显示，NB具有较低的突变负荷和频发突变。NB表现为携带较多的基因组结构性变异，是其发生、发展的重要驱动因素。临床上已将MYCN扩增和11q缺失等基因组结构性变异纳入风险分组中，但目前对于NB基因组结构性变异的了解与NB的生物学、临床复杂性仍存在差距。高通量基因组学技术的发展推动了研究者对NB基因组特征尤其是结构性变异特征有了更加全面的认识，为探索NB发生、发展机制以及更加精细的风险分层提供了数据基础。本文就近年来NB的基因组结构性变异特征研究进展进行综述。
- 神经母细胞瘤 /
- 基因组特征 /
- 结构变异 /
- 预后价值
Abstract: Neuroblastoma (NB) is an embryonic malignancy arising from the neural crest cells of the sympathetic nervous system. It exhibits a high degree of biological and clinical heterogeneity. Genome sequencing studies have shown that NB has a low mutational load and few recurrent mutations. However, NB exhibits a high number of genomic structural variants, which are important drivers of tumorigenesis and progression. Genomic structural variants, such as MYCN amplification and 11q deletion, have been used as biomarkers for risk stratification in clinical practice. Nevertheless, a gap still exists between the understanding of genomic structural variants in NB and its biological and clinical heterogeneity. The development of high-throughput genomics technologies has promoted a more comprehensive understanding of the genomic features of NB, especially its structural variants. Further understanding of the involvement of these genomic characteristics in tumorigenesis and progression will help clarify risk stratification. In this paper, we review the current research on characterization of genomic structural variant in NB.
- neuroblastoma (NB) /
- genomic characteristics /
- structural variation /
- prognostic value

HTML全文

参考文献(32)

[1]	Pugh TJ, Morozova O, Attiyeh EF, et al. The genetic landscape of high-risk neuroblastoma[J]. Nat Genet, 2013, 45(3):279-284. doi: 10.1038/ng.2529
[2]	Schramm A, Köster J, Assenov Y, et al. Mutational dynamics between primary and relapse neuroblastomas[J]. Nat Genet, 2015, 47(8):872-877. doi: 10.1038/ng.3349
[3]	Lopez G, Conkrite KL, Doepner M, et al. Somatic structural variation targets neurodevelopmental genes and identifies SHANK2 as a tumor suppressor in neuroblastoma[J]. Genome Res, 2020, 30(9):1228-1242. doi: 10.1101/gr.252106.119
[4]	Brady SW, Liu YL, Ma XT, et al. Pan-neuroblastoma analysis reveals age- and signature-associated driver alterations[J]. Nat Commun, 2020, 11(1):5183. doi: 10.1038/s41467-020-18987-4
[5]	Qiu B, Matthay KK. Advancing therapy for neuroblastoma[J]. Nat Rev Clin Oncol, 2022, 19(8):515-533. doi: 10.1038/s41571-022-00643-z
[6]	Rickman DS, Schulte JH, Eilers M. The expanding world of N-MYC-driven tumors[J]. Cancer Discov, 2018, 8(2):150-163. doi: 10.1158/2159-8290.CD-17-0273
[7]	Otte J, Dyberg C, Pepich A, et al. MYCN function in neuroblastoma development[J]. Front Oncol, 2020, 10:624079.
[8]	Zimmerman MW, Liu Y, He SN, et al. MYC drives a subset of high-risk pediatric neuroblastomas and is activated through mechanisms including enhancer hijacking and focal enhancer amplification[J]. Cancer Discov, 2018, 8(3):320-335. doi: 10.1158/2159-8290.CD-17-0993
[9]	Rosswog C, Fassunke J, Ernst A, et al. Genomic ALK alterations in primary and relapsed neuroblastoma[J]. Br J Cancer, 2023, 128(8):1559-1571.
[10]	Bellini A, Pötschger U, Bernard V, et al. Frequency and prognostic impact of ALK amplifications and mutations in the European neuroblastoma study group (SIOPEN) high-risk neuroblastoma trial (HR-NBL1)[J]. J Clin Oncol, 2021, 39(30):3377-3390. doi: 10.1200/JCO.21.00086
[11]	Schulte JH, Eggert A. ALK Inhibitors in neuroblastoma: a sprint from bench to bedside[J]. Clin Cancer Res, 2021, 27(13):3507-3509.
[12]	D'Oto A, Fang J, Jin HJ, et al. KDM6B promotes activation of the oncogenic CDK4/6-pRB-E2F pathway by maintaining enhancer activity in MYCN^-amplified neuroblastoma[J]. Nat Commun, 2021, 12(1):7204. doi: 10.1038/s41467-021-27502-2
[13]	Aygun N. Biological and genetic features of neuroblastoma and their clinical importance[J]. Curr Pediatr Rev, 2018, 14(2):73-90. doi: 10.2174/1573396314666180129101627
[14]	Yue ZX, Xing TY, Zhao W, et al. MYCN amplification plus 1p36 loss of heterozygosity predicts ultra high risk in bone marrow metastatic neuroblastoma[J]. Cancer Med, 2022, 11(8):1837-1849. doi: 10.1002/cam4.4583
[15]	García-López J, Wallace K, Otero JH, et al. Large 1p36 deletions affecting Arid1a locus facilitate mycn-driven oncogenesis in neuroblastoma[J]. Cell Rep, 2020, 30(2):454-464. doi: 10.1016/j.celrep.2019.12.048
[16]	Valentijn LJ, Koster J, Zwijnenburg DA, et al. TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors[J]. Nat Genet, 2015, 47(12):1411-1414. doi: 10.1038/ng.3438
[17]	Molenaar JJ, Koster J, Zwijnenburg DA, et al. Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes[J]. Nature, 2012, 483(7391):589-593. doi: 10.1038/nature10910
[18]	Verhaak RGW, Bafna V, Mischel PS. Extrachromosomal oncogene amplification in tumour pathogenesis and evolution[J]. Nat Rev Cancer, 2019, 19(5):283-288. doi: 10.1038/s41568-019-0128-6
[19]	Koche RP, Rodriguez-Fos E, Helmsauer K, et al. Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma[J]. Nat Genet, 2020, 52(1):29-34.
[20]	Helmsauer K, Valieva ME, Ali S, et al. Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma[J]. Nat Commun, 2020, 11(1):5823. doi: 10.1038/s41467-020-19452-y
[21]	Paolini L, Hussain S, Galardy PJ. Chromosome instability in neuroblastoma: a pathway to aggressive disease[J]. Front Oncol, 2022, 12:988972. doi: 10.3389/fonc.2022.988972
[22]	de Bernardi B, Di Cataldo A, Garaventa A, et al. Stage 4 s neuroblastoma: features, management and outcome of 268 cases from the Italian Neuroblastoma Registry[J]. Ital J Pediatr, 2019, 45(1):8. doi: 10.1186/s13052-018-0599-1
[23]	Janoueix-Lerosey I, Schleiermacher G, Michels E, et al. Overall genomic pattern is a predictor of outcome in neuroblastoma[J]. J Clin Oncol, 2009, 27(7):1026-1033. doi: 10.1200/JCO.2008.16.0630
[24]	Schleiermacher G, Janoueix-Lerosey I, Ribeiro A, et al. Accumulation of segmental alterations determines progression in neuroblastoma[J]. J Clin Oncol, 2010, 28(19):3122-3130. doi: 10.1200/JCO.2009.26.7955
[25]	Ackermann S, Cartolano M, Hero B, et al. A mechanistic classification of clinical phenotypes in neuroblastoma[J]. Science, 2018, 362(6419):1165-1170. doi: 10.1126/science.aat6768
[26]	Peifer M, Hertwig F, Roels F, et al. Telomerase activation by genomic rearrangements in high-risk neuroblastoma[J]. Nature, 2015, 526(7575):700-704. doi: 10.1038/nature14980
[27]	Roderwieser A, Sand F, Walter E, et al. Telomerase is a prognostic marker of poor outcome and a therapeutic target in neuroblastoma[J]. JCO Precis Oncol, 2019, 3:1-20.
[28]	Yu EY, Zahid SS, Aloe S, et al. Reciprocal impacts of telomerase activity and ADRN/MES differentiation state in neuroblastoma tumor biology[J]. Commun Biol, 2021, 4(1):1315. doi: 10.1038/s42003-021-02821-8
[29]	Hartlieb SA, Sieverling L, Nadler-Holly M, et al. Alternative lengthening of telomeres in childhood neuroblastoma from genome to proteome[J]. Nat Commun, 2021, 12(1):1269. doi: 10.1038/s41467-021-21247-8
[30]	Cheung NK, Zhang JH, Lu C, et al. Association of age at diagnosis and genetic mutations in patients with neuroblastoma[J]. JAMA, 2012, 307(10):1062-1071. doi: 10.1001/jama.2012.228
[31]	Qadeer ZA, Valle-Garcia D, Hasson D, et al. ATRX In-frame fusion neuroblastoma is sensitive to EZH2 inhibition via modulation of neuronal gene signatures[J]. Cancer Cell, 2019, 36(5):512-527. doi: 10.1016/j.ccell.2019.09.002
[32]	George SL, Parmar V, Lorenzi F, et al. Novel therapeutic strategies targeting telomere maintenance mechanisms in high-risk neuroblastoma[J]. J Exp Clin Cancer Res, 2020, 39(1):78. doi: 10.1186/s13046-020-01582-2