Vízkeleti Laura, Ecsedi Szilvia, Rákosy Zsuzsa, Orosz Adrienn, Lázár Viktória, Emri Gabriella, Koroknai Viktória, Kiss Tímea, Ádány Róza, Balázs Margit
Department of Preventive Medicine, Faculty of Public Health, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Tumour Biol. 2012 Dec;33(6):2189-99. doi: 10.1007/s13277-012-0480-6. Epub 2012 Sep 23.
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.
已有充分证据表明,细胞周期蛋白D1(CCND1)扩增在肢端型皮肤恶性黑色素瘤中是常见事件;然而,其在该疾病其他亚型中的作用仍存在争议。本研究的目的是评估CCND1的基因和表达改变,重点关注原发性皮肤黑色素瘤,确定BRAF和NRAS的突变状态,并将数据与临床病理参数相关联。CCND1扩增与溃疡形成及转移部位有关。在校正BRAF和NRAS基因的突变状态后,未发生此类突变的样本中的CCND1扩增与溃疡形成和阳光暴露有关。细胞周期蛋白D1(CCND1)mRNA水平在多发转移灶中降低,且与BRAF和NRAS基因的mRNA水平及突变状态均相关。具有BRAF(V600)或NRAS(Q61)突变的原发性黑色素瘤表现出较低的CCND1 mRNA水平。CCND1蛋白表达与Breslow厚度、转移灶形成及较短的生存时间相关。这些观察结果表明,CCND1改变与黑色素瘤进展相关,并受BRAF和NRAS突变的影响。我们的数据表明,CCND1扩增在皮肤黑色素瘤中可能具有预后意义,并突出显示CCND1基因表达改变可能影响转移进展、生存及转移部位。