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
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