title: Investigation of IGF2/ApaI and H19/RsaI polymorphisms in patients with cutaneous melanoma.
abstract: OBJECTIVE
  The etiology of cutaneous melanoma is complex, involving both heterogeneous genetic and environmental components. The aim of our study was to verify if single polymorphic sites within IGF2 and H19 genes and their consequent haplotypes influence risk and/or prognosis of familial melanoma.
  
  
  METHODS
  Twenty one patients with clinical criteria of hereditary melanoma (early onset, presence of multiple primary melanoma, and/or one or more affected first- or second-degree relatives) and previously screened for CDKN2A mutations were genotyped by IGF2/ApaI and H19/RsaI PCR-RFLPs. Data were compared between patients and a control group (100 healthy young individuals) using Chi-square and Fisher's exact tests. We also investigated if these polymorphic sites could be microRNAs potential targets, using RegRNA software.
  
  
  RESULTS
  Although the IGF2 and H19 genotypes/haplotypes were not significantly associated with melanoma, two of the most severe cases (very early onset or multiple melanomas) showed to be heterozygous for both genes. We found an overlap between IGF2/ApaI and miR-615-5p, and between H19/RsaI and miR-574-3p.
  
  
  CONCLUSIONS
  Some studies have shown H19, and IGF2 genes (or related genes or protein, for example, IGF2R and IMP-3) differential expression in melanoma. However, no study has attempted to examine markers across this cluster in relation to melanoma until now. Since the base change may impair the pairing of microRNA and its binding site, our results suggest a new window for future studies of IGF2 and H19 genetic variability and posttranscriptional regulation. Due to the importance and based on the present results, we suggest that the genotype/haplotype analysis of IGF2 and H19 polymorphisms should be better investigated in large populations with cutaneous melanoma, attempting to tie the association with progression of the disease.
authors.affiliation: Department of Gynecology and Obstetrics, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: M R
authors.initials: MR
authors.lastname: Soares
authors.forename: J
authors.initials: J
authors.lastname: Huber
authors.forename: A F L
authors.initials: AF
authors.lastname: Rios
authors.forename: E S
authors.initials: ES
authors.lastname: Ramos
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D015252:Deoxyribonucleases, Type II Site-Specific; D016147:Genes, Tumor Suppressor; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II; D015252:Deoxyribonucleases, Type II Site-Specific; C038485:GGGCCC-specific type II deoxyribonucleases; C040158:GTAC-specific type II deoxyribonucleases