The role of omics in neuroblastoma: Patient’s risk classification and personalised therapy

Maria Rosaria Esposito, Sanja Aveic, Anke Seydel, Gian Paolo Tonini

Abstract


Neuroblastoma is an embryonic malignancy of early childhood that originates from neural crest cells and shows heterogeneous biological, morphological, genetic, and clinical characteristics. MYCN oncogene amplification has been observed in 20% of neuroblastoma cases and is one of the most reliable prognostic markers of this tumour. In the last decade, microarray comparative genomic hybridization (CGH) has been widely employed to discover genome abnormalities and to evaluate patient’s risk. Several numerical and structural copy number variations including the loss of 1p, 3p, 9p, 11q, and 14q, along with the gain of 2p and 17q, was observed to be mainly associated with high-risk neuroblastoma. Extensive studies have been carried out to identify gene signatures associated with tumour progression and at least two gene signatures, the 59-gene and the 146-gene, can be used to significantly discriminate between low- and high-risk patients. Subsequently, the advent of next-generation sequencing has shown that neuroblastoma is characterised by a low number of damaging somatic mutations. Furthermore, mutations occurring in ALKATRX, and TERT genes play a crucial role in neuroblastoma development. This raises the possibility of performing next-generation sequencing signature to refine a patient’s risk classification. Omics data have allowed us to improve the diagnostic of neuroblastoma and to identify biological targets that are suitable for precision medicine. The present review highlights the paramount importance of omics in neuroblastoma and updates the most recent advances in this area that are associated with personalised medicine of patients with neuroblastoma.


Keywords


genomic alterations; next-generation sequencing; neuroblastoma; omics; personalised medicine; targeted therapy

Full Text:

PDF

References


Maris JM, Hogarty MD, Bagatell R, Cohn SL. Neuro-blastoma. Lancet 2007; 369(9579): 2106–2120. doi: 10. 1016/S0140-6736(07)60983-0.

Brodeur GM. Neuroblastoma: Biological insights into a clinical enigma. Nat Rev Cancer 2003; 3(3): 203–216. doi: 10.1038/nrc1014.

Maris JM. Recent advances in neuroblastoma. N Engl J Med 2010; 362(23): 2202–2011. doi: 10.1056/NEJMra0804577.

Brodeur GM, Maris JM, Yamashiro DJ, Hogarty MD, White PS. Biology and genetics of human neuroblastomas. J Pediatr Hematol Oncol 1997; 19(2): 93–101. doi: 10.1097/00043426-199703000-00001.

Shimada H. Tumors of the neuroblastoma group. Pathol-ogy (Phila) 1993; 2(1): 43–59.

Cohn SL, Pearson AD, London WB, Monclair T, Ambros PF, Brodeur GM, et al. The International Neuroblastoma Risk Group (INRG) classification system: An INRG Task Force report. J Clin Oncol 2009; 27(2): 289–297. doi: 10. 1200/JCO.2008.16.6785.

Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, et al. The International Neuroblastoma Pathology Classifica-tion (the Shimada system). Cancer 1999; 86(2): 364– 372. doi: 10.1002/(SICI)1097-0142(19990715)86:2<364::AID- CNCR21>3.0.CO;2-7.

Pinto NR, Applebaum MA, Volchenboum SL, Matthay KK, London WB, et al. Advances in risk classification and treatment strategies for neuroblastoma. J Clin Oncol 2015; 33(27): 3008–3017. doi: 10.1200/JCO.2014.59.4648.

Maris JM. The biologic basis for neuroblastoma hetero-geneity and risk stratification. Curr Opin Pediatr 2005; 17(1): 7–13. doi: 10.1097/01.mop.0000150631.60571.89.

Trochet D, Bourdeaut F, Janoueix-Lerosey I, Deville A, de Pontual L, et al. Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma. Am J Hum Genet 2004; 74(4): 761–764. doi: 10.1086/383253.

Perri P, Bachetti T, Longo L, Matera I, Seri M, et al. PHOX2B mutations and genetic predisposition to neuro-blastoma. Oncogene 2005; 24(18): 3050–3053. doi: 10. 1038/sj.onc.1208532.

Longo L, Panza E, Schena F, Seri M, Devoto M, et al. Genetic predisposition to familial neuroblastoma: Identi-fication of two novel genomic regions at 2p and 12p. Hum Hered 2007; 63(3–4): 205–211. doi: 10.1159/000099997.

Chen Y, Takita J, Choi YL, Kato M, Ohira M, et al. On-cogenic mutations of ALK kinase in neuroblastoma. Nature 2008; 455(7215): 971–974. doi: 10.1038/nature07399.

George RE, Sanda T, Hanna M, Fröhling S, Luther W 2nd, et al. Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature 2008; 455(7215): 975– 978. doi: 10.1038/nature07397.

Janoueix-Lerosey I, Lequin D, Brugières L, Ribeiro A, de Pontual L, et al. Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma. Nature 2008; 455(7215): 967–970. doi: 10.1038/nature07398.

Mossé YP, Laudenslager M, Longo L, Cole KA, Wood A, et al. Identification of ALK as a major familial neuro-blastoma predisposition gene. Nature 2008; 455(7215): 930–935. doi: 10.1038/nature07261.

De Mariano M, Gallesio R, Chierici M, Furlanello C, Conte M, et al. Identification of GALNT14 as a novel neuroblastoma predisposition gene. Oncotarget 2015; 6(28): 26335–26346. doi: 10.18632/oncotarget.4501.

Schwab M, Alitalo K, Klempnauer KH, Varmus HE, Bishop JM, et al. Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblas-toma cell lines and a neuroblastoma tumour. Nature 1983; 305(5931): 245–248. doi: 10.1038/305245a0.

Seeger RC, Brodeur GM, Sather H, Dalton A, Siegel SE, et al. Association of multiple copies of the N-myc onco-gene with rapid progression of neuroblastomas. N Engl J Med 1985; 313(18): 1111–1116. doi: 10.1056/NEJM198-5103¬13131802.

Łastowska M, Van Roy N, Bown N, Speleman F, Roberts P, et al. Molecular cytogenetic definition of 17q translo-cation breakpoints in neuroblastoma. Med Pediatr Oncol 2001; 36(1): 20–23. doi: 10.1002/1096-911X(20010101) 36:1<20::AID-MPO1006>3.0.CO;2-E.

Plantaz D, Vandesompele J, Van Roy N, Łastowska M, Bown N, et al. Comparative genomic hybridization (CGH) analysis of stage 4 neuroblastoma reveals high frequency of 11q deletion in tumors lacking MYCN amplification. Int J Cancer 2001; 91(5): 680–686. doi: 10.1002/1097- 0215(200002)9999:9999<::AID-IJC1114>3.0.CO;2-R.

Scaruffi P, Coco S, Cifuentes F, Albino D, Nair M, et al. Identification and characterization of DNA imbalances in neuroblastoma by high-resolution oligonucleotide array comparative genomic hybridization. Cancer Genet Cyto-genet 2007; 177(1): 20–29. doi: 10.1016/j.cancergencyto. 2007.05.002.

Janoueix-Lerosey I, Schleiermacher G, Michels E, Mos-seri V, Ribeiro A, et al. Overall genomic pattern is a pre-dictor of outcome in neuroblastoma. J Clin Oncol 2009; 27(7): 1026–1033. doi: 10.1200/JCO.2008.16.0630.

Schleiermacher G, Mosseri V, London WB, Maris JM, Brodeur GM, et al. Segmental chromosomal alterations have prognostic impact in neuroblastoma: A report from the INRG project. Br J Cancer 2012; 107(8): 1418–1422. doi: 10.1038/bjc.2012.375.

Cheung NK, Dyer MA. Neuroblastoma: Developmen-tal biology, cancer genomics and immunotherapy. Nat Rev Cancer 2013; 13(6): 397–411. doi: 10.1038/nrc3526.

Best CJ, Leiva IM, Chuaqui RF, Gillespie JW, Duray PH, et al. Molecular differentiation of high- and moder-ate-grade human prostate cancer by cDNA microarray analysis. Diagn Mol Pathol 2003; 12(2): 63–70.

van't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 2002; 415(6871): 530–536. doi: 10.1038/415530a.

Vasselli JR, Shih JH, Iyengar SR, Maranchie J, Riss J, et al. Predicting survival in patients with metastatic kidney cancer by gene-expression profiling in the primary tumor. Proc Natl Acad Sci USA 2003; 100(12): 6958–6963. doi: 10.1073/pnas.1131754100.

Khan J, Wei JS, Ringner M, Saal LH, Ladanyi M, et al. Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks. Nat Med 2001; 7(6): 673–679. doi: 10.1038/89044.

Asgharzadeh S, Pique-Regi R, Sposto R, Wang H, Yang Y, et al. Prognostic significance of gene expression profiles of metastatic neuroblastomas lacking MYCN gene ampli-fication. J Natl Cancer Inst 2006; 98(17): 1193–1203. doi: 10.1093/jnci/djj330.

Oberthuer A, Berthold F, Warnat P, Hero B, Kahlert Y, et al. Customized oligonucleotide microarray gene expres-sion-based classification of neuroblastoma patients out-performs current clinical risk stratification. J Clin Oncol 2006; 24(31): 5070–5078. doi: 10.1200/JCO.2006.06.1879.

Oberthuer A, Hero B, Berthold F, Juraeva D, Faldum A, et al. Prognostic impact of gene expression-based classi-fication for neuroblastoma. J Clin Oncol 2010; 28(21): 3506–3515. doi: 10.1200/JCO.2009.27.3367.

Ohira M, Oba S, Nakamura Y, Isogai E, Kaneko S, et al. Expression profiling using a tumor-specific cDNA mi-croarray predicts the prognosis of intermediate risk neu-roblastomas. Cancer Cell 2005; 7(4): 337–350. doi: 10. 1016/j.ccr.2005.03.019.

Vermeulen J, De Preter K, Naranjo A, Vercruysse L, Van Roy N, et al. Predicting outcomes for children with neu-roblastoma using a multigene-expression signature: A retrospective SIOPEN/COG/GPOH study. Lancet Oncol 2009; 10(7): 663–671. doi: 10.1016/S1470-2045(09)70-154-8.

Wei JS, Greer BT, Westermann F, Steinberg SM, Son CG, et al. Prediction of clinical outcome using gene expression profiling and artificial neural networks for patients with neuroblastoma. Cancer Res 2004; 64(19): 6883– 6391. doi: 10.1158/0008-5472.CAN-04-0695.

De Preter K, Vermeulen J, Brors B, Delattre O, Eggert A, et al. Accurate outcome prediction in neuroblastoma across independent data sets using a multigene signature. Clin Cancer Res 2010; 16(5): 1532–1541. doi: 10.1158/ 1078-0432.CCR-09-2607.

Molenaar JJ, Koster J, Zwijnenburg DA, van Sluis P, Valentijn LJ, et al. Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes. Nature 2012; 483(7391): 589–593. doi: 10.1038/natu¬re10910.

Sausen M, Leary RJ, Jones S, Wu J, Reynolds CP, et al. Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma. Nat Genet 2013; 45(1): 12–17. doi: 10.1038/ng. 2493.

Lasorsa VA, Formicola D, Pignataro P, Cimmino F, Cala-brese FM, et al. Exome and deep sequencing of clinically aggressive neuroblastoma reveal somatic mutations that affect key pathways involved in cancer progression. On-cotarget 2016; 7(16): 21840–21852. doi: 10.18632/oncotarget.8187.

Pugh TJ, Morozova O, Attiyeh EF, Asgharzadeh S, Wei JS, et al. The genetic landscape of high-risk neuroblastoma. Nat Genet 2013; 45(3): 279–284. doi: 10.1038/ng. 2529.

Banerji S, Cibulskis K, Rangel-Escareno C, Brown KK, Carter SL, et al. Sequence analysis of mutations and translocations across breast cancer subtypes. Nature 2012; 486(7403): 405–409. doi: 10.1038/nature11154.

Cheung NK, Zhang J, Lu C, Parker M, Bahrami A, et al. Association of age at diagnosis and genetic mutations in patients with neuroblastoma. JAMA 2012; 307(10): 1062–1071. doi: 10.1001/jama.2012.228.

Peifer M, Hertwig F, Roels F, Dreidax D, Gartlgruber M, et al. Telomerase activation by genomic rearrangements in high-risk neuroblastoma. Nature 2015; 526(7575): 700–704. doi: 10.1038/nature14980.

Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, et al. TERT rearrangements are frequent in neu-roblastoma and identify aggressive tumors. Nat Genet 2015; 47(12): 1411–1414. doi: 10.1038/ng.3438.

Nik-Zainal S, Alexandrov LB, Wedge DC, Van Loo P, Greenman CD, et al. Mutational processes molding the genomes of 21 breast cancers. Cell 2012; 149(5): 979– 993. doi: 10.1016/j.cell.2012.04.024.

Bellini A, Bernard V, Leroy Q, Rio Frio T, Pierron G, et al. Deep sequencing reveals occurrence of subclonal ALK mutations in neuroblastoma at diagnosis. Clin Cancer Res 2015; 21(21): 4913–4921. doi: 10.1158/1078-0432.CCR-15-0423.

Robert C, Schachter J, Long GV, Arance A, Grob JJ, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015; 372(26): 2521–2532. doi: 10.1056/NEJMoa1503093.

Feder MK, Gilbert F. Clonal evolution in a human neuro-blastoma. J Natl Cancer Inst 1983; 70(6): 1051–1056.

Gotoh T, Sugihara H, Matsumura T, Katsura K, Takamatsu T, et al. Human neuroblastoma demonstrating clonal evolution in vivo. Genes Chromosomes Cancer 1998; 22(1): 42–49. doi: 10.1002/(SICI)1098-2264(199805)22:1<42:: AID-GCC6>3.0.CO;2-7.

Mora J, Cheung NK, Gerald WL. Genetic heterogeneity and clonal evolution in neuroblastoma. Br J Cancer 2001; 85(2): 182–189. doi: 10.1054/bjoc.2001.1849.

Tonini GP, Verdona G, Garaventa A, Cornaglia-Ferraris P. Antiblastic treatment does not affect N-myc gene amplif¬i¬c-ation in neuroblastoma. Anticancer Res 1987; 7(4B): ¬729-–732.

Eleveld TF, Oldridge DA, Bernard V, Koster J, Daage LC, et al. Relapsed neuroblastomas show frequent RAS- MAPK pathway mutations. Nat Genet 2015; 47(8): 864– 871. doi: 10.1038/ng.3333.

Schramm A, Köster J, Assenov Y, Althoff K, Peifer M, et al. Mutational dynamics between primary and relapse neu-roblastomas. Nat Genet 2015; 47(8): 872–877. doi: 10.1038/ng.3349.

Gustafson WC, Matthay KK. Progress towards personal-ised therapeutics: Biologic- and risk-directed therapy for neuroblastoma. Expert Rev Neurother 2011; 11(10): 1411–1423. doi: 10.1586/ern.11.103.

Ambros PF, Ambros IM, Brodeur GM, Haber M, Khan J, et al. International consensus for neuroblastoma molecular diagnostics: Report from the International Neuroblastoma Risk Group (INRG) Biology Committee. Br J Cancer 2009; 100(9): 1471–1482. doi: 10.1038/sj.bjc. 6605014.

Beiske K, Burchill SA, Cheung IY, Hiyama E, Seeger RC, et al. Consensus criteria for sensitive detection of minimal neuroblastoma cells in bone marrow, blood and stem cell preparations by immunocytology and QRT-PCR: Recommendations by the International Neuroblastoma Risk Group Task Force. Br J Cancer 2009; 100(10): 1627–1637. doi: 10.1038/sj.bjc.6605029.

Brisse HJ, McCarville MB, Granata C, Krug KB, Woot-ton-Gorges SL, et al. Guidelines for imaging and staging of neuroblastic tumors: Consensus report from the Inter-national Neuroblastoma Risk Group Project. Radiology 2011; 261(1): 243–257. doi: 10.1148/radiol.11101352.

Matthay KK, Shulkin B, Ladenstein R, Michon J, Giam-marile F, et al. Criteria for evaluation of disease extent by 123I-metaiodobenzylguanidine scans in neuroblastoma: A report for the International Neuroblastoma Risk Group (INRG) Task Force. Br J Cancer 2010; 102(9): 1319– 1326. doi: 10.1038/sj.bjc.6605621.




DOI: http://dx.doi.org/10.30564/amor.v2i5.81

Refbacks

  • There are currently no refbacks.


Copyright (c) 2018 Maria Rosaria Esposito, Sanja Aveic, Anke Seydel, Gian Paolo Tonini

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.