neuroblastomas
Image Gallery
Defeinition: 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
Molecular biology
gene amplifications
-
MYCN gene amplification
- 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
CGH (16075461)
CGH Gains
| 2p24 | MYCN |
| 17q23 |
CGH Losses
| 1p32.1 | |||
| 1p36.3 | 25%-52% | ||
| 3p21.31-3p22.1 | |||
| 5q35.2-5q35.3 | |||
| 7q31.2 | 31% | ||
| 7q34 | 31% | ||
| 8qcen-q24 | 26% | ||
| 9q21-9q24.1 | 26% | ||
| 10p11-p15 | 40% | ||
| 10q26.11-10q26.12 | |||
| 11q23-25 | 42% | ||
| 12q24.1 | 26% | ||
| 14q32 | 37% | ||
| 16q23.1-16q24.3 | |||
| 18q21.32-18q23 | |||
| 19q | 31% | 20p11.21-20p11.23 |
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
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
See also
neuroblastic tumors
- neuroblastoma
- ganglioneuroblastoma
- ganglioneuroma
References
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. Integrative genomics identifies distinct molecular classes of neuroblastoma and shows that multiple genes are targeted by regional alterations in DNA copy number. Cancer Res. 2006 Jun 15;66(12):6050-62. PMID: 16778177
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
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
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