Dataset Information

Prevalence of variations in melanoma susceptibility genes among Slovenian melanoma families.

ABSTRACT: BACKGROUND: Two high-risk genes have been implicated in the development of CM (cutaneous melanoma). Germline mutations of the CDKN2A gene are found in < 25% of melanoma-prone families and there are only seven families with mutation of the CDK4 gene reported to date. Beside those high penetrance genes, certain allelic variants of the MC1R gene modify the risk of developing the disease. THE AIMS OF OUR STUDY WERE: to determine the prevalence of germline CDKN2A mutations and variants in members of families with familial CM and in patients with multiple primary CM; to search for possible CDK4 mutations, and to determine the frequency of variations in the MC1R gene. METHODS: From January 2001 until January 2007, 64 individuals were included in the study. The group included 28 patients and 7 healthy relatives belonging to 25 families, 26 patients with multiple primary tumors and 3 children with CM. Additionally 54 healthy individuals were included as a control group. Mutations and variants of the melanoma susceptibility genes were identified by direct sequencing. RESULTS: Seven families with CDKN2A mutations were discovered (7/25 or 28.0%). The L94Q mutation found in one family had not been previously reported in other populations. The D84N variant, with possible biological impact, was discovered in the case of patient without family history but with multiple primary CM. Only one mutation carrier was found in the control group. Further analysis revealed that c.540C>T heterozygous carriers were more common in the group of CM patients and their healthy relatives (11/64 vs. 2/54). One p14ARF variant was discovered in the control group and no mutations of the CDK4 gene were found. Most frequently found variants of the MC1R gene were T314T, V60L, V92M, R151C, R160W and R163Q with frequencies slightly higher in the group of patients and their relatives than in the group of controls, but the difference was statistically insignificant. CONCLUSION: The present study has shown high prevalence of p16INK4A mutations in Slovenian population of familial melanoma patients (37%) and an absence of p14ARF or CDK4 mutations.

SUBMITTER: Peric B

PROVIDER: S-EPMC2556318 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Prevalence of variations in melanoma susceptibility genes among Slovenian melanoma families.

Peric Barbara B Cerkovnik Petra P Novakovic Srdjan S Zgajnar Janez J Besic Nikola N Hocevar Marko M

BMC medical genetics 20080919

<h4>Background</h4>Two high-risk genes have been implicated in the development of CM (cutaneous melanoma). Germline mutations of the CDKN2A gene are found in < 25% of melanoma-prone families and there are only seven families with mutation of the CDK4 gene reported to date. Beside those high penetrance genes, certain allelic variants of the MC1R gene modify the risk of developing the disease.<h4>The aims of our study were</h4>to determine the prevalence of germline CDKN2A mutations and variants i ...[more]

PMID: 18803811

Similar Datasets

Project description:BackgroundMelanoma is an aggressive type of skin cancer whose aetiology remains elusive as both environmental and genetic factors can contribute to its development. Recent studies have demonstrated the existence of multiple copies of E2F1 gene in melanoma specimens which could explain the deregulated E2F1 activity in this type of cancer. This finding suggests a key role for this transcription factor in the malignant transformation of melanocytes. Therefore, E2F1 has been considered as a potential therapeutic target for this form of skin cancer. Since germline copy number variations (CNVs) have been associated with increased susceptibility to different types of cancer, the aim of our study was to assess germline E2F1 CNV in melanoma patients. However, CNVs not necessarily lead to gene dosage imbalance, hence, further factors, in association with CNVs, could contribute to clinical manifestations. Considering that heat stress has been hypothesised as a contributing factor to skin cancer, we also investigated the effect of heat stress on E2F1 expression.MethodsE2F1 CNV was measured in genomic DNA isolated from blood of 552 patients diagnosed with melanoma and 520 healthy subjects using TaqMan Copy Number Assays. E2F1 mRNA expression was also evaluated by RT-qPCR in the melanoma cell line, SK MEL 267, before and after exposure to heat stress.ResultsWe found that patients diagnosed with melanoma (1.6%, 9/552) harboured frequently altered germline E2F1 copies compared to healthy subjects (0%, 0/520). Moreover, the difference among the two groups was statistically significant (p = 0.004). Furthermore, we found that heat exposure alone can significantly induce E2F1 expression.ConclusionsThis is the first study that shows a relation between germline E2F1 CNV and melanoma, suggesting that altered copies of this gene might be a predisposing factor to skin cancer. Our results also suggest that environmental insults, such as heat stress, could contribute to an aberrant E2F1 activity by inducing E2F1 mRNA expression. Therefore, subjects with multiple constitutive copies of E2F1 are at greater risk of developing melanoma when exposed to heat. Altogether our results corroborate with the hypothesis that susceptibility to melanoma depends on both the environment and genetic factors.

Dataset Information

Prevalence of variations in melanoma susceptibility genes among Slovenian melanoma families.

Publications

Prevalence of variations in melanoma susceptibility genes among Slovenian melanoma families.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets