title: The role of CCND1 alterations during the progression of cutaneous malignant melanoma.
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.
authors.affiliation: Department of Preventive Medicine, Faculty of Public Health, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Laura
authors.initials: L
authors.lastname: Vízkeleti
authors.forename: Szilvia
authors.initials: S
authors.lastname: Ecsedi
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Rákosy
authors.forename: Adrienn
authors.initials: A
authors.lastname: Orosz
authors.forename: Viktória
authors.initials: V
authors.lastname: Lázár
authors.forename: Gabriella
authors.initials: G
authors.lastname: Emri
authors.forename: Viktória
authors.initials: V
authors.lastname: Koroknai
authors.forename: Tímea
authors.initials: T
authors.lastname: Kiss
authors.forename: Róza
authors.initials: R
authors.lastname: Ádány
authors.forename: Margit
authors.initials: M
authors.lastname: Balázs
mesh_terms: D000328:Adult; D055028:Comparative Genomic Hybridization; D019938:Cyclin D1 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D055815:Young Adult
chemical_list: C530104:CCND1 protein, human; D012333:RNA, Messenger; D019938:Cyclin D1; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf