Skip to main page content
U.S. flag
See More

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2010 Jun 10;362(23):2202-11.
doi: 10.1056/NEJMra0804577.

Recent advances in neuroblastoma

John M Maris  1
Affiliations
Review

Recent advances in neuroblastoma

John M Maris. N Engl J Med. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Dr. Maris reports receiving grants from GlaxoSmithKline and Merck and being a named investigator on two pending U.S. patents for methods to identify neuroblastomas, for which he has not received royalties. No other potential conflict of interest relevant to this article was reported.

Figures

Figure 1
Figure 1. Clinical Presentations of Neuroblastoma
Neuroblastoma is a childhood cancer that is diagnosed at a median age of about 17 months. Tumors can arise anywhere along the sympathetic nervous system, with the majority occurring in the adrenal medulla. Primary tumors in the neck or upper chest can cause Horner’s syndrome (ptosis, miosis, and anhidrosis). Tumors along the spinal column can expand through the intraforaminal spaces and cause cord compression, with resulting paralysis. Although many lower-stage neuroblastomas are encapsulated and can be surgically excised with little chance of complications, higher-stage tumors often infiltrate local organ structures, surround critical nerves and vessels such as the celiac axis, and are largely unresectable at the time of diagnosis. Neuroblastomas typically metastasize to regional lymph nodes and to the bone marrow by means of the hematopoietic system. Tumor cells metastatic to marrow can infiltrate cortical bone. Neuroblastomas also can metastasize to the liver, most notably in patients with stage 4S tumors, in whom involvement can be extensive; however, transient and complete regression often occurs with no intervention other than supportive care.
Figure 2
Figure 2. Model of Genetic Susceptibility to Neuroblastoma
The y axis indicates the theoretical relative risk of neuroblastoma, and the x axis indicates the number of known and theoretical susceptibility alleles. A genetic threshold for the development of disease has been postulated, and malignant transformation is probably modified by interactions related to environmental exposure. A mutation in the ALK or PHOX2B gene results in a single, highly penetrant risk allele that allows developing neuroblastic tissue to meet or exceed this threshold for malignant transformation. These types of mutations are powerful enough to permit neuroblastoma to occur within families as a mendelian trait. On the other hand, there are multiple common DNA variations (polymorphisms) in a large number of genes that cooperate to reach this threshold in patients without ALK or PHOX2B mutations. For these sporadic cases of neuroblastoma, an excessive inheritance of “risk” variants has been postulated that increases susceptibility to the disease. Discovered susceptibility genes include FLJ22536, BARD1, and NBPF23. The total number of susceptibility loci is not currently known, nor is it known whether these polymorphisms act in an additive or synergistic (epistatic) fashion.
Figure 3
Figure 3. Genomic Basis of Neuroblastoma Risk Groups
Two broad neuroblastoma phenotypes — aggressive and benign — are seen clinically, with the latter showing a high propensity for spontaneous regression or differentiation. These two groups are largely identifiable at a chromosomal level by the presence of segmental aberrations (translocations, amplifications, and deletions) in the more aggressive cases and by whole-chromosome gains in the more benign cases. Thus, the International Neuroblastoma Risk Group (INRG) classification is related to these chromosomal alterations, but the current system is imprecise, since the intermediate group in particular remains poorly defined. Current investigation is focused on the identification of molecular predictors of outcome in the high-risk group (as well as in patients with aggressive neuroblastomas masquerading as more benign forms of the disease).
See this image and copyright information in PMC

References

    1. Hoehner JC, Gestblom C, Hedborg F, Sandstedt B, Olsen L, Pahlman S. A developmental model of neuroblastoma: differentiating stroma-poor tumors’ progress along an extra-adrenal chromaffin lineage. Lab Invest. 1996;75:659–75. - PubMed
    1. London WB, Castleberry RP, Matthay KK, et al. Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children’s Oncology Group. J Clin Oncol. 2005;23:6459–65. - PubMed
    1. Ries LAG, Smith MA, Gurney JG, et al. Cancer incidence and survival among children and adolescents: United States SEER program 1975–1995. Bethesda, MD: National Cancer Institute; 1999. (NIH publication no. 99–4649.)
    1. Carlsen NL. How frequent is spontaneous remission of neuroblastomas? Implications for screening. Br J Cancer. 1990;61:441–6. - PMC - PubMed
    1. Cole WH, Everson TC. Spontaneous regression of cancer: preliminary report. Ann Surg. 1956;144:366–83. - PMC - PubMed

Publication types