Estudio de las mutaciones en el gen de Telomerasa transcriptasa inversa (TERT) y su valor pronóstico en gliomas

IDH (isocitrate dehydrogenase) gene mutations are present in the majority of low-grade diffuse gliomas and define the clinicopathological nucleus of the respective morphologically defined entities. On the contrary, according to the WHO classification of 2016, the majority of glioblastomas belong to...

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Autor principal: Moggia, Daniela
Otros Autores: Wilda, Maximiliano
Formato: Tesis de maestría acceptedVersion
Lenguaje:Español
Publicado: Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica 2023
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Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_7806
https://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_7806.dir/7806.PDF
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id I28-R145-HWA_7806
record_format dspace
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-145
collection Repositorio Digital de la Universidad de Buenos Aires (UBA)
language Español
orig_language_str_mv spa
topic Glioma difuso
Mutaciones en promotor de TERT
Mutaciones en el gen IDH1
Diagnóstico integrado
Diffuse glioma
TERT promoter mutations
Mutations in the IDH1 gene
Integrated diagnosis
Ciencias de la vida
spellingShingle Glioma difuso
Mutaciones en promotor de TERT
Mutaciones en el gen IDH1
Diagnóstico integrado
Diffuse glioma
TERT promoter mutations
Mutations in the IDH1 gene
Integrated diagnosis
Ciencias de la vida
Moggia, Daniela
Estudio de las mutaciones en el gen de Telomerasa transcriptasa inversa (TERT) y su valor pronóstico en gliomas
topic_facet Glioma difuso
Mutaciones en promotor de TERT
Mutaciones en el gen IDH1
Diagnóstico integrado
Diffuse glioma
TERT promoter mutations
Mutations in the IDH1 gene
Integrated diagnosis
Ciencias de la vida
description IDH (isocitrate dehydrogenase) gene mutations are present in the majority of low-grade diffuse gliomas and define the clinicopathological nucleus of the respective morphologically defined entities. On the contrary, according to the WHO classification of 2016, the majority of glioblastomas belong to the category IDH-wild (wildtype), which is defined by exclusion. TERT gene mutations (telomerase reverse transcriptase gene) have been suggested as a molecular marker for primary glioblastomas. We analyzed the molecular, histopathological and clinical profiles of a series of 17 diffuse gliomas (WHO grades II-IV) diagnosed and operated in the Sanatorium Anchorena, in which an analysis of TERT gene promoter mutations was performed as part of a research study in the Department of Genetics of the Hospital de Clínicas, CABA, Argentina. The tumors had already been sequenced to assess the status of the IDH1 gene and that information was available.\nMutations in the TERT gene promoter were present in 41% of the tumors (7 of the total of 17) and in 42% of the cases carrying the wild-type (wt) IDH1 gene (5 of 12). It was observed that all patients (except two) who carried mutations in the TERT gene had the wild-type IDH1 gene. Therefore, we can say that the mutations in the TERT gene promoter are inversely correlated with the mutations observed in the IDH1 gene which is a known molecular factor for a favorable prognosis. In 53% of cases (9 of the 17), a T> C polymorphism was identified in the TERT promoter at the -245 bp position (with respect to the ATG initiation codon) that could have an influence on glioma evolution . It was observed that mutations in the TERT gene promoter are correlated with grade IV glioma (4 patients with grade IV and 2 patients with grade II and III, not counting San). It was also found that mutations in the TERT gene promoter correlates with tumor growth and patient death. Thus it was seen that 4 of the 6 patients with mutations in the TERT promoter experienced tumor growth and / or death. It is concluded that mutations in the TERT gene promoter are molecular markers to take into account along with other biological changes to know the evolution of the tumor and the patient's life prognosis.
author2 Wilda, Maximiliano
author_facet Wilda, Maximiliano
Moggia, Daniela
format Tesis de maestría
Tesis de maestría
acceptedVersion
author Moggia, Daniela
author_sort Moggia, Daniela
title Estudio de las mutaciones en el gen de Telomerasa transcriptasa inversa (TERT) y su valor pronóstico en gliomas
title_short Estudio de las mutaciones en el gen de Telomerasa transcriptasa inversa (TERT) y su valor pronóstico en gliomas
title_full Estudio de las mutaciones en el gen de Telomerasa transcriptasa inversa (TERT) y su valor pronóstico en gliomas
title_fullStr Estudio de las mutaciones en el gen de Telomerasa transcriptasa inversa (TERT) y su valor pronóstico en gliomas
title_full_unstemmed Estudio de las mutaciones en el gen de Telomerasa transcriptasa inversa (TERT) y su valor pronóstico en gliomas
title_sort estudio de las mutaciones en el gen de telomerasa transcriptasa inversa (tert) y su valor pronóstico en gliomas
publisher Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica
publishDate 2023
url http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_7806
https://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_7806.dir/7806.PDF
work_keys_str_mv AT moggiadaniela estudiodelasmutacionesenelgendetelomerasatranscriptasainversatertysuvalorpronosticoengliomas
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spelling I28-R145-HWA_78062025-07-29 IDH (isocitrate dehydrogenase) gene mutations are present in the majority of low-grade diffuse gliomas and define the clinicopathological nucleus of the respective morphologically defined entities. On the contrary, according to the WHO classification of 2016, the majority of glioblastomas belong to the category IDH-wild (wildtype), which is defined by exclusion. TERT gene mutations (telomerase reverse transcriptase gene) have been suggested as a molecular marker for primary glioblastomas. We analyzed the molecular, histopathological and clinical profiles of a series of 17 diffuse gliomas (WHO grades II-IV) diagnosed and operated in the Sanatorium Anchorena, in which an analysis of TERT gene promoter mutations was performed as part of a research study in the Department of Genetics of the Hospital de Clínicas, CABA, Argentina. The tumors had already been sequenced to assess the status of the IDH1 gene and that information was available.\nMutations in the TERT gene promoter were present in 41% of the tumors (7 of the total of 17) and in 42% of the cases carrying the wild-type (wt) IDH1 gene (5 of 12). It was observed that all patients (except two) who carried mutations in the TERT gene had the wild-type IDH1 gene. Therefore, we can say that the mutations in the TERT gene promoter are inversely correlated with the mutations observed in the IDH1 gene which is a known molecular factor for a favorable prognosis. In 53% of cases (9 of the 17), a T> C polymorphism was identified in the TERT promoter at the -245 bp position (with respect to the ATG initiation codon) that could have an influence on glioma evolution . It was observed that mutations in the TERT gene promoter are correlated with grade IV glioma (4 patients with grade IV and 2 patients with grade II and III, not counting San). It was also found that mutations in the TERT gene promoter correlates with tumor growth and patient death. Thus it was seen that 4 of the 6 patients with mutations in the TERT promoter experienced tumor growth and / or death. It is concluded that mutations in the TERT gene promoter are molecular markers to take into account along with other biological changes to know the evolution of the tumor and the patient's life prognosis. Fil: Moggia, Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Buenos Aires, Argentina Wilda, Maximiliano Szijan, Irene Moggia, Daniela 2023-08-31 Las mutaciones del gen IDH (isocitrato deshidrogenasa) están presentes en la mayoría de los gliomas difusos de bajo grado y definen el núcleo clínico-patológico de las respectivas entidades definidas morfológicamente. Por el contrario, de acuerdo con la clasificación de la OMS del 2016, la mayoría de los glioblastomas pertenecen a la categoría IDH-salvaje (wild type), que se define por exclusión. Se han sugerido mutaciones del promotor en el gen de telomerasa transcriptasa inversa (TERT) como marcador molecular para glioblastomas primarios. Analizamos los perfiles moleculares, histopatológicos y clínicos de una serie de 17 gliomas difusos (grados II-IV de la OMS) diagnosticados y operados en el Sanatorio Anchorena, en los que se realizó un análisis de las mutaciones del promotor del gen TERT como parte de un estudio de investigación en la cátedra de Genética del hospital de Clínicas, CABA, Argentina. Los tumores ya habían sido secuenciados para evaluar el estado del gen IDH1 y se contaba con esa información.\nLas mutaciones en el promotor del gen TERT estuvieron presentes en el 41% de los tumores (7 del total de 17) y en 42 % de los casos que portaban el gen de IDH1 de tipo salvaje (wt) (5 de 12). Se pudo observar que todos los pacientes (excepto dos) que portaban mutaciones en el gen TERT presentaban el gen de IDH1 de tipo salvaje. Por lo tanto, podemos decir que las mutaciones en el promotor del gen TERT se correlacionan inversamente con las mutaciones observadas en el gen IDH1 que es un factor molecular conocido para un pronóstico favorable. En el 53% de los casos (9 de los 17), se identificó en el promotor de TERT un polimorfismo T>C en la posición -245 pb (con respecto al codón de iniciación ATG) que podría tener influencia en la evolución de glioma. Se observó que las mutaciones en el promotor del gen TERT están correlacionados con el grado IV de glioma (4 pacientes con grado IV y 2 pacientes con grado II y III, sin contar a San). También se encontró que las mutaciones en el promotor del gen TERT se correlacionan con el crecimiento del tumor y la muerte del paciente. Así se vió que 4 de los 6 pacientes con mutaciones en el promotor de TERT experimentaron crecimiento del tumor y/o muerte. Se concluye que las mutaciones en el promotor del gen TERT son marcadores moleculares para tener en cuenta junto con otros cambios biológicos para conocer la evolución del tumor y el pronóstico de vida del paciente. application/pdf Oubiña, José R. Quarleri, Jorge F. Surace, Ezequiel Glioma difuso Mutaciones en promotor de TERT Mutaciones en el gen IDH1 Diagnóstico integrado Diffuse glioma TERT promoter mutations Mutations in the IDH1 gene Integrated diagnosis spa Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Ciencias de la vida Magíster de la Universidad de Buenos Aires en Biología Molecular Médica Estudio de las mutaciones en el gen de Telomerasa transcriptasa inversa (TERT) y su valor pronóstico en gliomas info:eu-repo/semantics/masterThesis info:ar-repo/semantics/tesis de maestría info:eu-repo/semantics/acceptedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_7806 https://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_7806.dir/7806.PDF