Analysis of the miR-34a locus in 62 patients with familial cutaneous melanoma negative for CDKN2A/CDK4 screening

Angela M. Cozzolino, Lucia Pedace, Marco Castori, Paola De Simone, Nicoletta Preziosi, Isabella Sperduti, Chiara Panetta, Valerio Mogini, Carmelilia De Bernardo, Aldo Morrone, Caterina Catricala, Paola Grammatico

Research output: Contribution to journalArticlepeer-review

Abstract

MicroRNAs are small non-coding RNAs, which inhibit expression of specific target genes at the post-Transcriptional level and are often misregulated in human cancer. Among them, miR-34a is considered a tumor suppressor with a hypothetical role in melanoma tumorigenesis. In this work, 62 Italian index patients with familial melanoma and negative for CDKN2A/CDK4 screening were investigated for miR-34a germline mutations. Eight novel miR-34a sequence variants were identified at both the heterozygous (c.+259G>A, c.+424G>A, c.+1465C>T, c.+1769C>T, c.+2456T>G, c.+2603C>T, c.+2972T>A, c.+3069T>C) and homozygous (c.+424G>A, c.+1465C>T, c.+1769C>T) states. Molecular screening identified all nucleotide changes in a healthy population of 150 controls and demonstrated that they are common polymorphisms. However, statistically significant differences of allele and genotype frequencies were detected for c.+1465C>T and c.+1769C>T, and borderline values for c.+2456T>G. By stratifying patients by relevant clinical features (presence/absence of multiple primary melanoma, Breslow's thickness, phototype and number of nevi), no significant findings were noted except for an association between the c.+424G>A (heterozygous individual GA) and multiple primary melanoma and phototype III-IV. Our preliminary study suggests that miR-34a, although having a role in late tumorigenesis, does not contribute to the inherited susceptibility to cutaneous melanoma. A function as phenotypic modulator in familial melanoma cannot be excluded.

Original languageEnglish
Pages (from-to)201-208
Number of pages8
JournalFamilial Cancer
Volume11
Issue number2
DOIs
Publication statusPublished - Jun 2012

Keywords

  • Association studyFAM (familial melanoma)
  • MiRNA
  • MPM (multiple primary melanoma)
  • Mutation

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Oncology
  • Genetics(clinical)

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