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Rearrangements and increased expression of cyclin D1 (CCND1) in neuroblastoma

Jan J Molenaar1, Peter van Sluis, Kathy Boon

  • 1Department of Human Genetics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

Genes, Chromosomes & Cancer
|January 31, 2003
PubMed

Insights

Cyclin D1 (CCND1) is overexpressed in some neuroblastomas, suggesting its deregulation contributes to tumor development. Researchers found high CCND1 mRNA and protein levels, with some tumors showing CCND1 gene amplification or rearrangement.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Cycle Regulation

Background:

  • Cyclin D1 (CCND1) controls cell cycle progression and is often deregulated in cancers.
  • Neuroblastoma typically lacks consistent G1 cell cycle checkpoint aberrations.

Purpose of the Study:

  • To investigate the potential deregulation of cyclin D1 (CCND1) in neuroblastoma.
  • To determine if CCND1 overexpression or genetic alterations play a role in neuroblastoma tumorigenesis.

Main Methods:

  • Serial Analysis of Gene Expression (SAGE) for mRNA profiling.
  • Northern blot analysis for CCND1 expression.
  • Screening for CCND1 gene amplifications and rearrangements.

Main Results:

  • High CCND1 mRNA expression was observed in a subset of neuroblastoma cell lines and tumors (up to 0.3% of total mRNA).
  • Relative CCND1 overexpression was confirmed in 16/23 cell lines and 10/15 tumors, correlating with elevated protein levels.
  • CCND1 gene amplifications were found in 5/202 samples, and a rearrangement in 1/96 tumors.

Conclusions:

  • Relative overexpression of CCND1 occurs in neuroblastoma.
  • Clonal aberrations of CCND1, alongside high expression, suggest its deregulated activity contributes to neuroblastoma development.

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