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Increased C-MYC copy numbers on the background of CDKN2A loss is associated with improved survival in nodular melanoma

Abstract

Purpose

In order to obtain better insight into the genetic background of nodular melanoma (NM), we aimed to analyse the frequency of CDKN2A and C-MYC copy number changes. The impact of these aberrations on the metastatic potential and patient’s survival was considered.

Methods

Fluorescent in situ hybridization was used to analyse the C-MYC and CDKN2A genes on isolated nuclei from 49 paraffin-embedded primary NMs.

Results

Thirty-six (73.47%) melanoma samples showed CDKN2A deletion while 11 of these 36 (22.45%) additionally displayed C-MYC increased copy numbers. Cases positive for metastases more commonly displayed CDKN2A deletions. However, the combined C-MYC and CDKN2A aberrations were found predominantly in the non-metastasizing group of primary NM. The survival analysis furthermore demonstrated that patients with combined CDKN2A and C-MYC aberrations have a significantly better prognosis than carriers of CDKN2A deletion only.

Conclusions

We conclude that the C-MYC increased copy number changes on the background of CDKN2A deletions seem to be related to a low metastatic potential and better patients’ outcome in primary NMs.

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Acknowledgment

We thank Aat Mulder for technical support. The work of D. Koynova study was supported by the Marie Curie Research Training Grant; Contract no. QLGA-CT-2000-60005 and by the grant of the Ministry of Education and Science—Upgrading Of Research Infrastructure no. 05/01.08.2005. N. Gruis is a recipient of an ASPASIA fellowship of the Netherlands Organization for Scientific Research.

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Correspondence to Nelleke Gruis.

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Koynova, D., Jordanova, E., Kukutsch, N. et al. Increased C-MYC copy numbers on the background of CDKN2A loss is associated with improved survival in nodular melanoma. J Cancer Res Clin Oncol 133, 117–123 (2007). https://doi.org/10.1007/s00432-006-0150-4

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Keywords

  • Primary nodular melanoma
  • FISH
  • Paraffin material
  • CDKN2A deletion
  • C-MYC gain