Neuroblastoma

Effect of genetic factors on prognosis and treatment

G. M. Brodeur, C. Azar, M. Brother, Jill Reiter, B. Kaufman, H. Marshall, J. Moley, A. Nakagawara, R. Saylors, N. Scavarda, S. Schneider, J. Wasson, P. White, R. Seeger, T. Look, R. Castleberry

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

Background and Methods. Genetic analysis of tumor tissue has provided considerable insight into mechanisms of malignant transformation and progression. Neuroblastomas have been studied by cytogenetics, flow cytometry, and molecular genetic techniques, and these studies have identified several specific abnormalities that allow subclassification of these tumors into genetic/clinical subtypes. Results and Discussion. Four genetic abnormalities have been identified that are characteristic of certain neuroblastomas. These include: (1) loss of heterozygosity (LOH) for the short arm of chromosome 1, including band 1p36; (2) amplification of the N-myc protooncogene; (3) hyperdiploidy, or near triploidy; and (4) defects in expression or function of the nerve growth factor receptor (NGFR). Abnormalities of the NGFR are found in virtually all neuroblastoma cell lines, and some primary tumors. The latter have not been studied extensively. Hyperdiploidy is associated with lower stages of disease and with a favorable outcome in infants. LOH for chromosome 1, band p36, and N-myc amplification are more common in patients older than 1 year of age with advanced stages of disease. The latter two genetic abnormalities may be related, and LOH for 1p36 may precede the development of amplification. When these abnormalities are combined with assessment of DNA content, three distinct genetic subsets of neuroblastomas can be identified. The first is characterized by a hyperdiploid or near-triploid modal karyotype, with few if any cytogenetic rearrangements. These patients generally are younger than 1 year of age with localized disease and a good prognosis. The second has a near-diploid karyotype, with no consistent abnormality identified currently. These patients generally are older with more advanced stages of disease that progress slowly and are often fatal. The third group has a near-diploid or tetraploid karyotype, with deletions or LOH for 1p36, amplification of N-myc; or both. These patients generally are older with advanced stages of disease that rapidly are progressive. Thus, genetic analysis of neuroblastoma cells provides information that has prognostic significance and can direct a more appropriate choice of treatment.

Original languageEnglish (US)
Pages (from-to)1685-1694
Number of pages10
JournalCancer
Volume70
Issue number6 SUPPL.
StatePublished - 1992
Externally publishedYes

Fingerprint

Neuroblastoma
Loss of Heterozygosity
Polyploidy
Karyotype
Nerve Growth Factor Receptor
Triploidy
Chromosomes, Human, Pair 1
Diploidy
Cytogenetics
Therapeutics
Genetic Techniques
Neoplasms
Tetraploidy
Molecular Biology
Flow Cytometry
Cell Line
DNA

Keywords

  • deletion of chromosome 1p
  • loss of heterozygosity (LOH)
  • molecular genetics
  • N-myc amplification
  • neuroblastoma
  • NGF receptor (NGFR)
  • oncogenes
  • prognostic factors
  • suppressor genes
  • tumor cell DNA content

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Brodeur, G. M., Azar, C., Brother, M., Reiter, J., Kaufman, B., Marshall, H., ... Castleberry, R. (1992). Neuroblastoma: Effect of genetic factors on prognosis and treatment. Cancer, 70(6 SUPPL.), 1685-1694.

Neuroblastoma : Effect of genetic factors on prognosis and treatment. / Brodeur, G. M.; Azar, C.; Brother, M.; Reiter, Jill; Kaufman, B.; Marshall, H.; Moley, J.; Nakagawara, A.; Saylors, R.; Scavarda, N.; Schneider, S.; Wasson, J.; White, P.; Seeger, R.; Look, T.; Castleberry, R.

In: Cancer, Vol. 70, No. 6 SUPPL., 1992, p. 1685-1694.

Research output: Contribution to journalArticle

Brodeur, GM, Azar, C, Brother, M, Reiter, J, Kaufman, B, Marshall, H, Moley, J, Nakagawara, A, Saylors, R, Scavarda, N, Schneider, S, Wasson, J, White, P, Seeger, R, Look, T & Castleberry, R 1992, 'Neuroblastoma: Effect of genetic factors on prognosis and treatment', Cancer, vol. 70, no. 6 SUPPL., pp. 1685-1694.
Brodeur GM, Azar C, Brother M, Reiter J, Kaufman B, Marshall H et al. Neuroblastoma: Effect of genetic factors on prognosis and treatment. Cancer. 1992;70(6 SUPPL.):1685-1694.
Brodeur, G. M. ; Azar, C. ; Brother, M. ; Reiter, Jill ; Kaufman, B. ; Marshall, H. ; Moley, J. ; Nakagawara, A. ; Saylors, R. ; Scavarda, N. ; Schneider, S. ; Wasson, J. ; White, P. ; Seeger, R. ; Look, T. ; Castleberry, R. / Neuroblastoma : Effect of genetic factors on prognosis and treatment. In: Cancer. 1992 ; Vol. 70, No. 6 SUPPL. pp. 1685-1694.
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AU - Kaufman, B.

AU - Marshall, H.

AU - Moley, J.

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AU - Saylors, R.

AU - Scavarda, N.

AU - Schneider, S.

AU - Wasson, J.

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AU - Look, T.

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