Vista Equipo: Genetic-molecular study of the egfr/ pi3k/akt pathway in high and low grade gliomas

Genetic-molecular study of the egfr/ pi3k/akt pathway in high and low grade gliomas

Gliomas account for 70% of all central nervous system (CNS) tumors and are classified according to the WHO in low (I and II) or high (III and IV or glioblastoma multiforme, GBM) grade malignancies. The survival of patients with a high grade is less than 2 years. The EGFR/PI3K/AKT pathway promotes ce...

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Autores Principales:	Erira, Alveiro, Penagos, Jose, Zubieta, Camilo, Velandia, Fernando, Arboleda, Humberto, Arboleda Gonzalo
Formato:	Objeto de conferencia (Conference Object)
Lenguaje:	Inglés (English)
Publicado:	Elsevier 2010
Materias:	Medical and Health Sciences Oncology and Carcinogenesis
Acceso en línea:	https://repository.urosario.edu.co/handle/10336/26484 https://doi.org/10.1016/j.cancergencyto.2010.07.077

id	ir-10336-26484
recordtype	dspace
spelling	ir-10336-264842020-08-06T16:24:11Z Genetic-molecular study of the egfr/ pi3k/akt pathway in high and low grade gliomas Estudio genético-molecular de la vía egfr / pi3k / akt en gliomas de alto y bajo grado Erira, Alveiro Penagos, Jose Zubieta, Camilo Velandia, Fernando Arboleda, Humberto Arboleda Gonzalo Medical and Health Sciences Oncology and Carcinogenesis Gliomas account for 70% of all central nervous system (CNS) tumors and are classified according to the WHO in low (I and II) or high (III and IV or glioblastoma multiforme, GBM) grade malignancies. The survival of patients with a high grade is less than 2 years. The EGFR/PI3K/AKT pathway promotes cellular survival, inhibits apoptosis and differentiation. This pathway is regulated by phosphatase homologous of tensin (PTEN). In gliomas, amplification of EGFR and PI3K has been reported, as well as mutations in PI3KCA and PTEN, which are associated with permanent activation of this signaling pathway and with decreased expression of pro-apoptotic genes such as Bax and increased expression of anti-apoptotic genes such as Bcl2. We obtained 30 samples of gliomas with high and low grade. Amplification was assessed by real-time PCR with TaqMan probes for the EGFR, PI3K and AKT genes. Mutations in PI3KCA (9 and 20 exons) and PTEN (5 and 6 exons) were determined by direct sequencing from DNA using specific primers for each exon. The results of each sample were analyzed in 50 e30 and 30 e50 orientations using the program FINCH TV. Subsequent alignment was performed for each sample with the human reference sequence (obtained from Gene Bank) using the GENE RUNNER program. To assess the expression levels of the PI3K, AKT, Bax, and Bcl2 genes, cDNA obtained by reverse transcription was amplified by real-time PCR with SYBR Green using specific primers for each gene. The results were analyzed by calculating the CT. We did not find any high level EGFR amplifications. Only one grade IV sample showed an increase in gene dosage (2.8 times). PI3K was found amplified in 50% of grade I and II (0.4 times) and in 45% of grade III and IV (between 0.5 and 0.9 times). However, in 18% of the grade IV samples, the increase was greater than 1. AKT was not found amplified in the samples analyzed. Also, no mutations were found in PI3K and PTEN. In low-grade gliomas we found an increase (O1 time) in PI3K (62%), AKT (12.5%), Bcl2 (50%), and Bax (25%) gene expression. In highgrade tumors over-expression of PI3K (50%), AKT, Bcl2, and Bax (all 32%) was found. 2010-11 2020-08-06T16:24:08Z info:eu-repo/semantics/conferenceObject info:eu-repo/semantics/publishedVersion ISSN: 2210-7762 https://repository.urosario.edu.co/handle/10336/26484 https://doi.org/10.1016/j.cancergencyto.2010.07.077 eng info:eu-repo/semantics/restrictedAccess application/pdf Elsevier Cancer Genetics
institution	EdocUR - Universidad del Rosario
collection	DSpace
language	Inglés (English)
topic	Medical and Health Sciences Oncology and Carcinogenesis
spellingShingle	Medical and Health Sciences Oncology and Carcinogenesis Erira, Alveiro Penagos, Jose Zubieta, Camilo Velandia, Fernando Arboleda, Humberto Arboleda Gonzalo Genetic-molecular study of the egfr/ pi3k/akt pathway in high and low grade gliomas
description	Gliomas account for 70% of all central nervous system (CNS) tumors and are classified according to the WHO in low (I and II) or high (III and IV or glioblastoma multiforme, GBM) grade malignancies. The survival of patients with a high grade is less than 2 years. The EGFR/PI3K/AKT pathway promotes cellular survival, inhibits apoptosis and differentiation. This pathway is regulated by phosphatase homologous of tensin (PTEN). In gliomas, amplification of EGFR and PI3K has been reported, as well as mutations in PI3KCA and PTEN, which are associated with permanent activation of this signaling pathway and with decreased expression of pro-apoptotic genes such as Bax and increased expression of anti-apoptotic genes such as Bcl2. We obtained 30 samples of gliomas with high and low grade. Amplification was assessed by real-time PCR with TaqMan probes for the EGFR, PI3K and AKT genes. Mutations in PI3KCA (9 and 20 exons) and PTEN (5 and 6 exons) were determined by direct sequencing from DNA using specific primers for each exon. The results of each sample were analyzed in 50 e30 and 30 e50 orientations using the program FINCH TV. Subsequent alignment was performed for each sample with the human reference sequence (obtained from Gene Bank) using the GENE RUNNER program. To assess the expression levels of the PI3K, AKT, Bax, and Bcl2 genes, cDNA obtained by reverse transcription was amplified by real-time PCR with SYBR Green using specific primers for each gene. The results were analyzed by calculating the CT. We did not find any high level EGFR amplifications. Only one grade IV sample showed an increase in gene dosage (2.8 times). PI3K was found amplified in 50% of grade I and II (0.4 times) and in 45% of grade III and IV (between 0.5 and 0.9 times). However, in 18% of the grade IV samples, the increase was greater than 1. AKT was not found amplified in the samples analyzed. Also, no mutations were found in PI3K and PTEN. In low-grade gliomas we found an increase (O1 time) in PI3K (62%), AKT (12.5%), Bcl2 (50%), and Bax (25%) gene expression. In highgrade tumors over-expression of PI3K (50%), AKT, Bcl2, and Bax (all 32%) was found.
format	Objeto de conferencia (Conference Object)
author	Erira, Alveiro Penagos, Jose Zubieta, Camilo Velandia, Fernando Arboleda, Humberto Arboleda Gonzalo
author_facet	Erira, Alveiro Penagos, Jose Zubieta, Camilo Velandia, Fernando Arboleda, Humberto Arboleda Gonzalo
author_sort	Erira, Alveiro
title	Genetic-molecular study of the egfr/ pi3k/akt pathway in high and low grade gliomas
title_short	Genetic-molecular study of the egfr/ pi3k/akt pathway in high and low grade gliomas
title_full	Genetic-molecular study of the egfr/ pi3k/akt pathway in high and low grade gliomas
title_fullStr	Genetic-molecular study of the egfr/ pi3k/akt pathway in high and low grade gliomas
title_full_unstemmed	Genetic-molecular study of the egfr/ pi3k/akt pathway in high and low grade gliomas
title_sort	genetic-molecular study of the egfr/ pi3k/akt pathway in high and low grade gliomas
publisher	Elsevier
publishDate	2010
url	https://repository.urosario.edu.co/handle/10336/26484 https://doi.org/10.1016/j.cancergencyto.2010.07.077
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score	12,131701

Genetic-molecular study of the egfr/ pi3k/akt pathway in high and low grade gliomas

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