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Published in: Tumor Biology 6/2012

01-12-2012 | Research Article

The role of CCND1 alterations during the progression of cutaneous malignant melanoma

Authors: Laura Vízkeleti, Szilvia Ecsedi, Zsuzsa Rákosy, Adrienn Orosz, Viktória Lázár, Gabriella Emri, Viktória Koroknai, Tímea Kiss, Róza Ádány, Margit Balázs

Published in: Tumor Biology | Issue 6/2012

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Abstract

It is well demonstrated that CCND1 amplification is a frequent event in the acral subtype of cutaneous malignant melanoma; however, its role in the other subtypes of the disease is still controversial. The objectives of this study were to evaluate genetic and expression alterations of CCND1 with a focus on primary cutaneous melanomas, to define BRAF and NRAS mutation status, and correlate the data with clinical–pathological parameters. CCND1 amplification was associated with ulceration and the localization of the metastasis. After correction for the mutation state of BRAF and NRAS genes, CCND1 amplification in samples without such mutations was associated with ulceration and sun exposure. The cyclin D1 (CCND1) mRNA level decreased in lesions with multiple metastases and was correlated with both the mRNA levels and mutation state of BRAF and NRAS genes. Primary melanomas with BRAF V600 or NRAS Q61 mutations exhibited lower CCND1 mRNA level. CCND1 protein expression was associated with Breslow thickness, metastasis formation, and shorter survival time. These observations suggest that CCND1 alterations are linked to melanoma progression and are modified by BRAF and NRAS mutations. Our data show that CCND1 amplification could have a prognostic relevance in cutaneous melanoma and highlight that altered CCND1 gene expression may influence the metastatic progression, survival, and the localization of metastases.
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Metadata
Title
The role of CCND1 alterations during the progression of cutaneous malignant melanoma
Authors
Laura Vízkeleti
Szilvia Ecsedi
Zsuzsa Rákosy
Adrienn Orosz
Viktória Lázár
Gabriella Emri
Viktória Koroknai
Tímea Kiss
Róza Ádány
Margit Balázs
Publication date
01-12-2012
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 6/2012
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-012-0480-6

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