Home > G. Tumoral pathology > neuroblastoma
neuroblastoma
Saturday 19 July 2003
Digital cases
Case 223: Post-chemotherapy neuroblastic tumor
Definition: Poorly differentiated type of neuroblastic tumors.
Localization
soft tissue
- retroperitoneal region, paravertebral region
- mediastinum
- pelvic region (10813335)
- urachus (10382205)
urinary bladder (12891516, 11070482, 10224211)
Variants
undifferentiated neuroblastoma
poorly differentiated
differentiating
large cell neuroblastoma (14716776)
ganglioneuroblastoma
in situ neuroblastoma (16010489)
Age
neonatal neuroblastoma (fetal neuroblastoma)
infantile neuroblastoma
adult neuroblastoma
Cytognetics
constitutional translocation t(1;17)(p36;q12-21)
Ploidy
hyperdiploidy (or near triploidy)
- lower stages
- favorable outcome
Diploidy is a strong prognostic predictor of outcome.
Molecular biology
gene amplifications
-
MYCN gene amplification (MYCN-amplified neuroblastomas)
- amplification of N-myc (MYCN) in neuroblastoma is strongly correlated with loss of 1p36 and gain of 17q.
- more common in patients older than 1 year with advanced stages of the disease
gene mutations
- NME1 (NM23) somatic mutations in advanced neuroblastoma (MIM.15490)
gain of chromosome 17q
LOH - Allelotype: 11912152, 15892104
- 1p36 LOH
- 11q23 LOH (10490829)
CGH Gains
| 1q gain | |
| 2p24 gain | MYCN |
| 12q gain | |
| 17q23 gain |
CGH Losses
| 1p32.1 loss | |||
| 1p36.3 loss | 25%-52% | ||
| 3p21.31-3p22.1 loss | |||
| 4p loss | |||
| 5q35.2-5q35.3 loss | |||
| 7q31.2 loss | 31% | ||
| 7q34 loss | 31% | ||
| 8qcen-q24 loss | 26% | ||
| 9q21-9q24.1 loss | 26% | ||
| 10p11-p15 loss | 40% | ||
| 10q26.11-10q26.12 loss | |||
| 11q23-25 loss | 42% | ||
| 12q24.1 loss | 26% | ||
| 14q32 loss | 37% | ||
| 16q23.1-16q24.3 loss | |||
| 18q21.32-18q23 loss | |||
| 19q loss | 31% | 20p11.21-20p11.23 loss |
Genetic subsets (1325279)
1. hyperdiploid karyotype (or near-triploid karyotype)
2. near-diploid karyotype with no consistent anomalies
3. 1p36 LOH or MYCN amplification (or both) with near-diploid or tetraploid karyotype
A subset of tumors with a clinically benign phenotype showed predominantly whole chromosome gains and losses. (17647283)
Tumors with MYCN amplification had a unique genomic signature of 1p deletion and 17q gain, but few other rearrangements. (17647283)
Tumors with an aggressive clinical phenotype without MYCN amplification, showed multiple structural rearrangements. Most notable were deletions of 3p, 4p, and 11q and gain of 1q, 2p, 12q, and 17q. (17647283)
There is a subset of tumors with an aggressive clinical phenotype and no detectable DNA CNAs. (17647283)
Miscellaneous
schwannian cells and neuroblastic cells have the same genetic alterations ? (11107110, 11559566)
CpG-island hypermethylation of gene promoters: 14506696
Predisposition
abnormal constitutional karyotypes in patients with neuroblastoma
- mosaicism for monosomy 22
- constitutional 11q interstitial deletion (14662434, 14623457)
- pericentric inversion of chromosome 9 at band 9p21
- robertsonian translocation t(13;14)
- 47, XXX karyotype (14499703)
familial neuroblastoma (12880958)
probable excess of neuroblastoma in patients with Turner syndrome (14623457)
Constitutional chromosomal anomalies
mosaicism for monosomy 22
11q interstitial deletion
pericentric inversion of chromosome 9 at band 9p21
Robertsonian translocation t(13;14)
chromosomal rearrangements
- 1p36
- 2p23
- 3q
- 11q23
- 15q
- 1p
- 2p
- 9p
- 11q
- 16q
- 17q
Hypermethylation
Frequent promoter hypermethylation of RASSF1A and CASP8 in neuroblastoma (17064406)
See also
neuroblastic tumors
- neuroblastoma
- ganglioneuroblastoma
- ganglioneuroma
Pathology reviews
Joshi VV. Peripheral neuroblastic tumors: pathologic classification based on recommendations of international neuroblastoma pathology committee (Modification of shimada classification). Pediatr Dev Pathol. 2000 Mar-Apr;3(2):184-99. PMID: 10679039
References - CGH and genetics
Predicting outcomes for children with neuroblastoma using a multigene-expression signature: a retrospective SIOPEN/COG/GPOH study. Vermeulen J, De Preter K, Naranjo A, Vercruysse L, Van Roy N, Hellemans J, Swerts K, Bravo S, Scaruffi P, Tonini GP, De Bernardi B, Noguera R, Piqueras M, Cañete A, Castel V, Janoueix-Lerosey I, Delattre O, Schleiermacher G, Michon J, Combaret V, Fischer M, Oberthuer A, Ambros PF, Beiske K, Bénard J, Marques B, Rubie H, Kohler J, Pötschger U, Ladenstein R, Hogarty MD, McGrady P, London WB, Laureys G, Speleman F, Vandesompele J. Lancet Oncol. 2009 Jul;10(7):663-71. Epub 2009 Jun 8. PMID: 19515614
Overall genomic pattern is a predictor of outcome in neuroblastoma. Janoueix-Lerosey I, Schleiermacher G, Michels E, Mosseri V, Ribeiro A, Lequin D, Vermeulen J, Couturier J, Peuchmaur M, Valent A, Plantaz D, Rubie H, Valteau-Couanet D, Thomas C, Combaret V, Rousseau R, Eggert A, Michon J, Speleman F, Delattre O. J Clin Oncol. 2009 Mar 1;27(7):1026-33. PMID: 19171713
Microtubule-associated protein-2 is a sensitive marker of primary and metastatic neuroblastoma. Krishnan C, Higgins JP, West RB, Natkunam Y, Heerema-McKenney A, Arber DA. Am J Surg Pathol. 2009 Nov;33(11):1695-704. PMID: 19701075
ArrayCGH-based classification of neuroblastoma into genomic subgroups. Michels E, Vandesompele J, De Preter K, Hoebeeck J, Vermeulen J, Schramm A, Molenaar JJ, Menten B, Marques B, Stallings RL, Combaret V, Devalck C, De Paepe A, Versteeg R, Eggert A, Laureys G, Van Roy N, Speleman F. Genes Chromosomes Cancer. 2007 Sep 6; PMID: 17823929
Neuroblastomas have distinct genomic DNA profiles that predict clinical phenotype and regional gene expression. Mosse YP, Diskin SJ, Wasserman N, Rinaldi K, Attiyeh EF, Cole K, Jagannathan J, Bhambhani K, Winter C, Maris JM. Genes Chromosomes Cancer. 2007 Oct;46(10):936-49.
PMID: 17647283
Genome-Wide Analysis of Neuroblastomas using High-Density Single Nucleotide Polymorphism Arrays. George RE, Attiyeh EF, Li S, Moreau LA, Neuberg D, Li C, Fox EA, Meyerson M, Diller L, Fortina P, Look AT, Maris JM. PLoS ONE. 2007 Feb 28;2:e255. PMID: 17327916
High-resolution analysis of allelic imbalance in neuroblastoma cell lines by single nucleotide polymorphism arrays. Carr J, Bown NP, Case MC, Hall AG, Lunec J, Tweddle DA. Cancer Genet Cytogenet. 2007 Jan 15;172(2):127-38. PMID: 17213021
Oligonucleotide array-based comparative genomic hybridization (aCGH) of 90 neuroblastomas reveals aberration patterns closely associated with relapse pattern and outcome. Spitz R, Oberthuer A, Zapatka M, Brors B, Hero B, Ernestus K, Oestreich J, Fischer M, Simon T, Berthold F. Genes Chromosomes Cancer. 2006 Dec;45(12):1130-42. PMID: 16958102
Integrative genomics identifies distinct molecular classes of neuroblastoma and shows that multiple genes are targeted by regional alterations in DNA copy number. Wang Q, Diskin S, Rappaport E, Attiyeh E, Mosse Y, Shue D, Seiser E, Jagannathan J, Shusterman S, Bansal M, Khazi D, Winter C, Okawa E, Grant G, Cnaan A, Zhao H, Cheung NK, Gerald W, London W, Matthay KK, Brodeur GM, Maris JM. Cancer Res. 2006 Jun 15;66(12):6050-62. PMID: 16778177
Maris JM, Hii G, Gelfand CA, Varde S, White PS, Rappaport E, Surrey S, Fortina P. Region-specific detection of neuroblastoma loss of heterozygosity at multiple loci simultaneously using a SNP-based tag-array platform. Genome Res. 2005 Aug;15(8):1168-76. PMID: 16077016
Chen QR, Bilke S, Khan J. High-resolution cDNA microarray-based comparative genomic hybridization analysis in neuroblastoma. Cancer Lett. 2005 Oct 18;228(1-2):71-81. PMID: 15951107
Maris JM. The biologic basis for neuroblastoma heterogeneity and risk stratification. Curr Opin Pediatr. 2005 Feb;17(1):7-13. PMID: 15659956
Pahlman S, Stockhausen MT, Fredlund E, Axelson H. Notch signaling in neuroblastoma. Semin Cancer Biol. 2004 Oct;14(5):365-73. PMID: 15288262
Brodeur GM. Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer. 2003 Mar;3(3):203-16. PMID: 12612655
Vandesompele J, Speleman F, Van Roy N, Laureys G, Brinskchmidt C, Christiansen H, Lampert F, Lastowska M, Bown N, Pearson A, Nicholson JC, Ross F, Combaret V, Delattre O, Feuerstein BG, Plantaz D. Multicentre analysis of patterns of DNA gains and losses in 204 neuroblastoma tumors: how many genetic subgroups are there? Med Pediatr Oncol. 2001 Jan;36(1):5-10. PMID: 11464905
Maris JM, Matthay KK. Molecular biology of neuroblastoma. J Clin Oncol. 1999 Jul;17(7):2264-79. PMID: 10561284
Mora J, Cheung NK, Kushner BH, LaQuaglia MP, Kramer K, Fazzari M, Heller G, Chen L, Gerald WL. Clinical categories of neuroblastoma are associated with different patterns of loss of heterozygosity on chromosome arm 1p. J Mol Diagn. 2000 Feb;2(1):37-46. PMID: 11272900
Brodeur GM, Azar C, Brother M, Hiemstra J, Kaufman B, Marshall H, Moley J, Nakagawara A, Saylors R, Scavarda N, et al. Neuroblastoma. Effect of genetic factors on prognosis and treatment. Cancer. 1992 Sep 15;70(6 Suppl):1685-94. PMID: 1325279
