Single nucleotide polymorphism in PTEN-Long gene: a risk factor in chronic myeloid leukemia

Autor: Irene Larripa, C. Ferri, Natalia Weich, Ariela Freya Fundia, M.R. Bengió, Leandro German Gutierrez, P. Zapata, C. D. De Brasi
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Adult
Male
0301 basic medicine
CIENCIAS MÉDICAS Y DE LA SALUD
Population
Biotecnología relacionada con la Salud
Fusion Proteins
bcr-abl
Single-nucleotide polymorphism
Biology
Polymorphism
Single Nucleotide
PTEN-LONG
Biotecnología de la Salud
03 medical and health sciences
Exon
0302 clinical medicine
Gene Frequency
Risk Factors
Leukemia
Myelogenous
Chronic
BCR-ABL Positive
hemic and lymphatic diseases
Genetics
Humans
Protein Isoforms
PTEN
Tensin
Genetic Predisposition to Disease
Allele
education
Gene
Alleles
Aged
Aged
80 and over
education.field_of_study
CHRONIC MYELOID LEUKEMIA
Age Factors
PTEN Phosphohydrolase
Myeloid leukemia
General Medicine
Middle Aged
BCR-ABL1
POLYMORPHISM
030104 developmental biology
Case-Control Studies
030220 oncology & carcinogenesis
Mutation
Cancer research
biology.protein
Female
Signal Transduction
Zdroj: Repositorio Institucional Digital de la Universidad Nacional de Misiones (UNaM)
Universidad Nacional de Misiones
instacron:UNAM
ISSN: 1257-3787
Popis: Fil: Ferri, Cristian Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico (Nordeste). Instituto de Biotecnología Misiones. Laboratorio de Biotecnología Molecular; Argentina. Fil: Ferri, Cristian Alberto. Universidad Nacional de Misiones. Facultad de Ciencias Exactas Químicas y Naturales. Instituto Biotecnología Misiones. Laboratorio de Biotecnología Molecular; Argentina. Fil: Weich, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Laboratorio de Genética Hematológica; Argentina. Fil: Weich, Natalia. Academia Nacional de Medicina (Buenos Aires). Instituto de Medicina Experimental. Laboratorio de Genética Hematológica; Argentina. Fil: Weich, Natalia. Universidad de Miami. Facultad de Medicina Leonard M. Miller; Estados Unidos. Fil: Gutiérrez, L. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Laboratorio de Genética Hematológica; Argentina. Fil: Gutiérrez, L. Academia Nacional de Medicina (Buenos Aires). Instituto de Medicina Experimental. Laboratorio de Genética Hematológica; Argentina. Fil: De Brasi, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Laboratorio de Genética Hematológica; Argentina. Fil: De Brasi, Carlos Daniel. Academia Nacional de Medicina (Buenos Aires). Instituto de Medicina Experimental. Laboratorio de Genética Hematológica; Argentina. Fil: Bengió, M. R. Academia Nacional de Medicina (Buenos Aires). Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemato-oncología; Argentina. Fil: Zapata, Pedro Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico (Nordeste). Instituto de Biotecnología Misiones. Laboratorio de Biotecnología Molecular; Argentina. Fil: Zapata, Pedro Darío. Universidad Nacional de Misiones. Facultad de Ciencias Exactas Químicas y Naturales. Instituto Biotecnología Misiones. Laboratorio de Biotecnología Molecular; Argentina. Fil: Fundia, Ariela Freya. Academia Nacional de Medicina (Buenos Aires). Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemato-oncología; Argentina. Fil: Larripa, Irene Beatriz. Academia Nacional de Medicina (Buenos Aires). Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemato-oncología; Argentina. The BCR-ABL1 oncogene is associated with chronic myeloid leukemia (CML) pathogenesis, but the molecular mechanisms that initiate leukemogenesis are still unclear. Cancer pathogenesis has been associated with genetic alterations that may lead to inactivation of tumor suppressor genes. Phosphatase and tensin homolog (PTEN) is frequently deleted or inactivated in various tumors. A recently discovered variant of PTEN, PTEN-Long (PTEN-L), results from an alternative translation initiation site located upstream of the canonic AUG and generates a protein of 576 amino acids instead the expected protein of 403 amino acids. A 16 bp perfect palindromic motif centered on the PTEN-L CUG 513 start codon is required for translation initiation. A single nucleotide polymorphism (SNP) of PTEN-L gene rs12573787 is located on the first exon respect to the CUG initiation site. In this case-control study we evaluated the association of genetic variants in PTEN-L with CML risk and therapy response in the Argentine population. The allele A of SNP rs12573787 was found to be associated with CML risk OR (95% CI) 1.71 (1.11–2.63) p = 0.016, which resulted consistent by multivariate analysis adjusted by gender and age. According to previous evidence that CML is more frequent in males, we found that the genetic risk of CML was confined to this gender. Unexpectedly, we also found this association confined to CML patients older than 45 years old. To our knowledge, this is the first time that PTEN-L rs1257378 was studied in CML suggesting that the variant A allele is a risk factor for CML development but, no association with the failure to TKIs treatment was found.
Databáze: OpenAIRE
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