title: Analysis of the miR-34a locus in 62 patients with familial cutaneous melanoma negative for CDKN2A/CDK4 screening.
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.
authors.affiliation: Medical Genetics, Department of Molecular Medicine, San Camillo-Forlanini Hospital, Sapienza University, Circonvallazione Gianicolense, 87, 00152, Rome, Italy.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Cozzolino
authors.forename: Lucia
authors.initials: L
authors.lastname: Pedace
authors.forename: Marco
authors.initials: M
authors.lastname: Castori
authors.forename: Paola
authors.initials: P
authors.lastname: De Simone
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Preziosi
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.forename: Chiara
authors.initials: C
authors.lastname: Panetta
authors.forename: Valerio
authors.initials: V
authors.lastname: Mogini
authors.forename: Carmelilia
authors.initials: C
authors.lastname: De Bernardo
authors.forename: Aldo
authors.initials: A
authors.lastname: Morrone
authors.forename: Caterina
authors.initials: C
authors.lastname: Catricalà
authors.forename: Paola
authors.initials: P
authors.lastname: Grammatico
mesh_terms: D016022:Case-Control Studies; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D016147:Genes, Tumor Suppressor; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4