title: The role of AIRE polymorphisms in melanoma.
abstract: Polymorphisms of AIRE, a transcription factor that up-regulates intrathymic expression of tissue-specific antigens including melanoma-associated antigens (MAAs), may variably affect the selection of MAAs-specific thymocytes, generating T-cell repertoires protecting or predisposing individuals to melanoma. We found that AIRE single nucleotide polymorphisms (SNPs) rs1055311, rs1800520 and rs1800522 were significantly more frequent in healthy subjects than in melanoma patients, independently from sex, age and stages of melanoma. The presence of these SNPs was associated with increased frequency of two T-cell clonotypes specific for MAGE-1 linking their protective effect to selection/expansion of MAA-specific T cells. Interestingly, mRNA transcribed on the rs1800520 SNP showed increased free energy than the wild type suggesting that its reduced stability may be responsible for the different activity of the polymorphic AIRE molecule. This finding may contribute at identifying subjects with increased risk of developing melanoma or patients with melanoma that may take benefit from immunotherapy.
authors.affiliation: Center of Excellence for Biomedical Research, University of Genoa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Conteduca
authors.forename: F
authors.initials: F
authors.lastname: Ferrera
authors.forename: L
authors.initials: L
authors.lastname: Pastorino
authors.forename: D
authors.initials: D
authors.lastname: Fenoglio
authors.forename: S
authors.initials: S
authors.lastname: Negrini
authors.forename: M P
authors.initials: MP
authors.lastname: Sormani
authors.forename: F
authors.initials: F
authors.lastname: Indiveri
authors.forename: G Bianchi
authors.initials: GB
authors.lastname: Scarrà
authors.forename: G
authors.initials: G
authors.lastname: Filaci
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D019674:Genes, T-Cell Receptor beta / Q000235:genetics; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000235:genetics*; D058950:Melanoma-Specific Antigens; D008875:Middle Aged; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000235:genetics; D009690:Nucleic Acid Conformation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D012727:Sex Characteristics; D013816:Thermodynamics; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult; D000096927:AIRE Protein
chemical_list: D000951:Antigens, Neoplasm; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000096927:AIRE Protein; C072011:MAGEA1 protein, human