New Insights into the Genetics of Neuroblastoma

Overview

Journal Mol Diagn Ther

Specialties Molecular Biology
Pathology
Pharmacology

Date 2013 Jan 19

PMID 23329364

Citations 14

Authors

Srishma Sridhar

Batool Al-Moallem

Hawra Kamal

Marta Terrile

Raymond L Stallings

Affiliations

Soon will be listed here.

Abstract

Neuroblastoma is a genetically and clinically heterogeneous tumor of childhood, arising from precursor cells of the sympathetic nervous system. It is still a challenging cancer for pediatric oncology, as some tumors will spontaneously regress, while others will become refractory to all forms of therapy. The clinical course of this disease is greatly influenced by both patient age and the genetic abnormalities that occur within the tumors. MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian)) amplification and loss of chromosome 11q heterozygosity have been known to be indicative of poor prognosis. In this article, we review how mutations and structural alterations in specific genes contribute to inheritable predisposition to neuroblastoma and/or to aggressive disease pathogenesis, as well as implications for diagnosis and therapy. These genes include PHOX2B (paired-like homeobox 2b), ALK (anaplastic lymphoma receptor tyrosine kinase), and ATRX (alpha thalassemia/mental retardation syndrome X-linked).

Citing Articles

The Regulatory Mechanisms and Clinical Significance of Lnc SNHG4 in Cancer.

Pourghasem N, Ghorbanzadeh S, Nejatizadeh A Curr Pharm Des. 2022; 28(44):3563-3571.

PMID: 36411578 DOI: 10.2174/1381612829666221121161950.

Emerging Neuroblastoma 3D Models for Pre-Clinical Assessments.

Corallo D, Frabetti S, Candini O, Gregianin E, Dominici M, Fischer H Front Immunol. 2020; 11:584214.

PMID: 33324402 PMC: 7726254. DOI: 10.3389/fimmu.2020.584214.

Dendrimer Nanodevices and Gallic Acid as Novel Strategies to Fight Chemoresistance in Neuroblastoma Cells.

Alfei S, Marengo B, Zuccari G, Turrini F, Domenicotti C Nanomaterials (Basel). 2020; 10(6).

PMID: 32604768 PMC: 7353457. DOI: 10.3390/nano10061243.

miR-483-3p promotes proliferation and migration of neuroblastoma cells by targeting PUMA.

Wu K, Wang J, He J, Chen Q, Yang L Int J Clin Exp Pathol. 2020; 11(2):490-501.

PMID: 31938135 PMC: 6958035.

TP53BP2 decreases cell proliferation and induces autophagy in neuroblastoma cell lines.

Pang Y, Pan L, Zhang Y, Liu G Oncol Lett. 2019; 17(6):4976-4984.

PMID: 31186708 PMC: 6507348. DOI: 10.3892/ol.2019.10148.

References

Nair P, De Preter K, Depreter K, Vandesompele J, Speleman F, Stallings R . Aberrant splicing of the PTPRD gene mimics microdeletions identified at this locus in neuroblastomas. Genes Chromosomes Cancer. 2007; 47(3):197-202. DOI: 10.1002/gcc.20521. View

Vandesompele J, van Roy N, Van Gele M, Laureys G, Ambros P, Heimann P . Genetic heterogeneity of neuroblastoma studied by comparative genomic hybridization. Genes Chromosomes Cancer. 1998; 23(2):141-52. DOI: 10.1002/(sici)1098-2264(199810)23:2<141::aid-gcc7>3.0.co;2-2. View

Caren H, Abel F, Kogner P, Martinsson T . High incidence of DNA mutations and gene amplifications of the ALK gene in advanced sporadic neuroblastoma tumours. Biochem J. 2008; 416(2):153-9. DOI: 10.1042/bj20081834. View

Wong L, McGhie J, Sim M, Anderson M, Ahn S, Hannan R . ATRX interacts with H3.3 in maintaining telomere structural integrity in pluripotent embryonic stem cells. Genome Res. 2010; 20(3):351-60. PMC: 2840985. DOI: 10.1101/gr.101477.109. View

Schulte J, Bachmann H, Brockmeyer B, Depreter K, Oberthur A, Ackermann S . High ALK receptor tyrosine kinase expression supersedes ALK mutation as a determining factor of an unfavorable phenotype in primary neuroblastoma. Clin Cancer Res. 2011; 17(15):5082-92. DOI: 10.1158/1078-0432.CCR-10-2809. View

Sasaki T, Okuda K, Zheng W, Butrynski J, Capelletti M, Wang L . The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers. Cancer Res. 2010; 70(24):10038-43. PMC: 3045808. DOI: 10.1158/0008-5472.CAN-10-2956. View

Otto T, Horn S, Brockmann M, Eilers U, Schuttrumpf L, Popov N . Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma. Cancer Cell. 2008; 15(1):67-78. DOI: 10.1016/j.ccr.2008.12.005. View

Devoto M, Specchia C, Laudenslager M, Longo L, Hakonarson H, Maris J . Genome-wide linkage analysis to identify genetic modifiers of ALK mutation penetrance in familial neuroblastoma. Hum Hered. 2011; 71(2):135-9. PMC: 3136385. DOI: 10.1159/000324843. View

Mosse Y, Laudenslager M, Longo L, Cole K, Wood A, Attiyeh E . Identification of ALK as a major familial neuroblastoma predisposition gene. Nature. 2008; 455(7215):930-5. PMC: 2672043. DOI: 10.1038/nature07261. View

10.

Del Grosso F, De Mariano M, Passoni L, Luksch R, Tonini G, Longo L . Inhibition of N-linked glycosylation impairs ALK phosphorylation and disrupts pro-survival signaling in neuroblastoma cell lines. BMC Cancer. 2011; 11:525. PMC: 3267831. DOI: 10.1186/1471-2407-11-525. View

11.

Motegi A, Fujimoto J, Kotani M, Sakuraba H, Yamamoto T . ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth. J Cell Sci. 2004; 117(Pt 15):3319-29. DOI: 10.1242/jcs.01183. View

12.

Di Paolo D, Brignole C, Pastorino F, Carosio R, Zorzoli A, Rossi M . Neuroblastoma-targeted nanoparticles entrapping siRNA specifically knockdown ALK. Mol Ther. 2011; 19(6):1131-40. PMC: 3129808. DOI: 10.1038/mt.2011.54. View

13.

Brodeur G, Seeger R, Schwab M, Varmus H, Bishop J . Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science. 1984; 224(4653):1121-4. DOI: 10.1126/science.6719137. View

14.

Janoueix-Lerosey I, Schleiermacher G, Michels E, Mosseri V, Ribeiro A, Lequin D . Overall genomic pattern is a predictor of outcome in neuroblastoma. J Clin Oncol. 2009; 27(7):1026-33. DOI: 10.1200/JCO.2008.16.0630. View

15.

Mazot P, Cazes A, Boutterin M, Figueiredo A, Raynal V, Combaret V . The constitutive activity of the ALK mutated at positions F1174 or R1275 impairs receptor trafficking. Oncogene. 2011; 30(17):2017-25. DOI: 10.1038/onc.2010.595. View

16.

Heukamp L, Thor T, Schramm A, De Preter K, Kumps C, De Wilde B . Targeted expression of mutated ALK induces neuroblastoma in transgenic mice. Sci Transl Med. 2012; 4(141):141ra91. DOI: 10.1126/scitranslmed.3003967. View

17.

Li R, Morris S . Development of anaplastic lymphoma kinase (ALK) small-molecule inhibitors for cancer therapy. Med Res Rev. 2007; 28(3):372-412. DOI: 10.1002/med.20109. View

18.

George R, Sanda T, Hanna M, Frohling S, Luther 2nd W, Zhang J . Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature. 2008; 455(7215):975-8. PMC: 2587486. DOI: 10.1038/nature07397. View

19.

Chen Y, Takita J, Choi Y, Kato M, Ohira M, Sanada M . Oncogenic mutations of ALK kinase in neuroblastoma. Nature. 2008; 455(7215):971-4. DOI: 10.1038/nature07399. View

20.

Berry T, Luther W, Bhatnagar N, Jamin Y, Poon E, Sanda T . The ALK(F1174L) mutation potentiates the oncogenic activity of MYCN in neuroblastoma. Cancer Cell. 2012; 22(1):117-30. PMC: 3417812. DOI: 10.1016/j.ccr.2012.06.001. View