neuroblastomas
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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
- NME1 (NM23) somatic mutations in advanced neuroblastoma (MIM.15490)
gain of chromosome 17q
LOH - Allelotype: 11912152, 15892104
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
- neuroblastoma
- ganglioneuroblastoma
- ganglioneuroma
References
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. ArrayCGH-based classification of neuroblastoma into genomic subgroups. Genes Chromosomes Cancer. 2007 Sep 6; PMID: 17823929
Mosse YP, Diskin SJ, Wasserman N, Rinaldi K, Attiyeh EF, Cole K, Jagannathan J, Bhambhani K, Winter C, Maris JM. Neuroblastomas have distinct genomic DNA profiles that predict clinical phenotype and regional gene expression. Genes Chromosomes Cancer. 2007 Oct;46(10):936-49.
PMID: 17647283
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