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

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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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  • DOI: https://doi.org/10.1007/s00432-006-0150-4

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