The role of AIRE polymorphisms in melanoma
Autor: | Giuseppina Conteduca, Gilberto Filaci, Simone Negrini, Francesca Ferrera, G. Bianchi Scarrà, Daniela Fenoglio, Maria Pia Sormani, F. Indiveri, Lorenza Pastorino |
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Jazyk: | angličtina |
Rok vydání: | 2010 |
Předmět: |
Models
Molecular Male RNA Stability Messenger Gene Frequency Models Genotype Immunology and Allergy genetics Melanoma Sex Characteristics Homozygote Age Factors Single Nucleotide Middle Aged Neoplasm Proteins Genes T-Cell Receptor beta Thermodynamics Female Melanoma-Specific Antigens Adult Heterozygote Adolescent Immunology Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Young Adult Antigen Antigens Neoplasm medicine T-Cell Receptor beta SNP Humans RNA Messenger Antigens Polymorphism Aged Melanoma-associated antigen Wild type Cancer Molecular medicine.disease Adolescent Adult Age Factors Aged Antigens Neoplasm genetics Female Gene Frequency genetics Genes genetics Genotype Heterozygote Homozygote Humans Male Melanoma diagnosis/genetics Melanoma-Specific Antigens Middle Aged Models Molecular Neoplasm Proteins genetics Nucleic Acid Conformation Polymorphism genetics RNA Stability genetics RNA chemistry/genetics Sex Characteristics Thermodynamics Transcription Factors genetics Young Adult Genes chemistry/genetics Cancer research Nucleic Acid Conformation RNA diagnosis/genetics Transcription Factors |
Popis: | 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. |
Databáze: | OpenAIRE |
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