Polymorphisms in Pathways in Pediatric Astrocytomas
Central nervous system tumors, especially astrocytomas, are the solid neoplasms with the highest incidence and mortality rates in childhood. The diagnosis is based on histopathological characteristics, but molecular methods have been increasingly used. Translationally controlled tumor protein (TCTP)...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2023-01-01
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| Series: | ASN Neuro |
| Online Access: | https://doi.org/10.1177/17590914231153481 |
| _version_ | 1811166424474845184 |
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| author | Eduardo Morais de Castro Leonardo Vinícius Barbosa Aline Simoneti Fonseca Seigo Nagashima Caroline Busatta Vaz de Paula Rafaela Zeni Letícia Arianne Panini do Carmo Luciane Regina Cavalli Luiz Fernando Bleggi Torres Andrea Senff Ribeiro Lucia de Noronha Cleber Machado-Souza |
| author_facet | Eduardo Morais de Castro Leonardo Vinícius Barbosa Aline Simoneti Fonseca Seigo Nagashima Caroline Busatta Vaz de Paula Rafaela Zeni Letícia Arianne Panini do Carmo Luciane Regina Cavalli Luiz Fernando Bleggi Torres Andrea Senff Ribeiro Lucia de Noronha Cleber Machado-Souza |
| author_sort | Eduardo Morais de Castro |
| collection | DOAJ |
| description | Central nervous system tumors, especially astrocytomas, are the solid neoplasms with the highest incidence and mortality rates in childhood. The diagnosis is based on histopathological characteristics, but molecular methods have been increasingly used. Translationally controlled tumor protein (TCTP) protein, encoded by the tumor protein, translationally controlled 1 ( TPT1 ) gene, is a multifunctional protein with an important physiological role in the cell cycle. Expression of this protein has been associated with several neoplasms, including astrocytomas in adults. However, the role of this protein in pediatric astrocytomas is largely unknown. We aim to evaluate in cases of pediatric astrocytomas, the frequency of polymorphisms in the TPT1 gene and other genes associated with its molecular pathways, such as MTOR , MDM2 , TP53 , and CDKN1A , correlating it with protein expression and clinical variables, in formalin-fixed, paraffin-embedded (FFPE) samples. These samples were submitted to genotyping and immunohistochemistry analyses. The most revealing results refer to the MDM2 gene, rs117039649 [G/C], in which C polymorphic allele was observed only in the glioblastomas ( p = .028). The CDKN1A gene, rs3176334 [T/C] presented a homozygous polymorphic genotype only in high-grade astrocytomas, when infiltrating tumors were compared ( p = .039). The immunohistochemical expression of cytoplasmic MDM2 correlated with better survival rates in patients with glioblastoma ( p = .018). The presence of polymorphisms in the MDM2 and CDKN1A genes, as well as a specific correlation between MDM2 expression, suggests a likely association with risk in pediatric astrocytomas. This study sought the probable role involved in the TCTP pathway, and associated proteins, in the tumorigenesis of pediatric astrocytomas, and some could have potential impact as prognostic markers in these patients. |
| first_indexed | 2024-04-10T15:52:08Z |
| format | Article |
| id | doaj.art-cc596284eb4d477e85f7eb1a719f03b5 |
| institution | Directory Open Access Journal |
| issn | 1759-0914 |
| language | English |
| last_indexed | 2024-04-10T15:52:08Z |
| publishDate | 2023-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | ASN Neuro |
| spelling | doaj.art-cc596284eb4d477e85f7eb1a719f03b52023-02-11T03:03:24ZengSAGE PublishingASN Neuro1759-09142023-01-011510.1177/17590914231153481Polymorphisms in Pathways in Pediatric AstrocytomasEduardo Morais de Castro0Leonardo Vinícius Barbosa1Aline Simoneti Fonseca2Seigo Nagashima3Caroline Busatta Vaz de Paula4Rafaela Zeni5Letícia Arianne Panini do Carmo6Luciane Regina Cavalli7Luiz Fernando Bleggi Torres8Andrea Senff Ribeiro9Lucia de Noronha10Cleber Machado-Souza11 , , Curitiba, Paraná, Brazil , , Curitiba, Paraná, Brazil , , Curitiba, Paraná, Brazil , Curitiba, Paraná, Brazil , Curitiba, Paraná, Brazil , Curitiba, Paraná, Brazil , Curitiba, Paraná, Brazil , , Curitiba, Paraná, Brazil , Curitiba, Paraná, Brazil , Curitiba, Paraná, Brazil , Curitiba, Paraná, Brazil , , Curitiba, Paraná, BrazilCentral nervous system tumors, especially astrocytomas, are the solid neoplasms with the highest incidence and mortality rates in childhood. The diagnosis is based on histopathological characteristics, but molecular methods have been increasingly used. Translationally controlled tumor protein (TCTP) protein, encoded by the tumor protein, translationally controlled 1 ( TPT1 ) gene, is a multifunctional protein with an important physiological role in the cell cycle. Expression of this protein has been associated with several neoplasms, including astrocytomas in adults. However, the role of this protein in pediatric astrocytomas is largely unknown. We aim to evaluate in cases of pediatric astrocytomas, the frequency of polymorphisms in the TPT1 gene and other genes associated with its molecular pathways, such as MTOR , MDM2 , TP53 , and CDKN1A , correlating it with protein expression and clinical variables, in formalin-fixed, paraffin-embedded (FFPE) samples. These samples were submitted to genotyping and immunohistochemistry analyses. The most revealing results refer to the MDM2 gene, rs117039649 [G/C], in which C polymorphic allele was observed only in the glioblastomas ( p = .028). The CDKN1A gene, rs3176334 [T/C] presented a homozygous polymorphic genotype only in high-grade astrocytomas, when infiltrating tumors were compared ( p = .039). The immunohistochemical expression of cytoplasmic MDM2 correlated with better survival rates in patients with glioblastoma ( p = .018). The presence of polymorphisms in the MDM2 and CDKN1A genes, as well as a specific correlation between MDM2 expression, suggests a likely association with risk in pediatric astrocytomas. This study sought the probable role involved in the TCTP pathway, and associated proteins, in the tumorigenesis of pediatric astrocytomas, and some could have potential impact as prognostic markers in these patients.https://doi.org/10.1177/17590914231153481 |
| spellingShingle | Eduardo Morais de Castro Leonardo Vinícius Barbosa Aline Simoneti Fonseca Seigo Nagashima Caroline Busatta Vaz de Paula Rafaela Zeni Letícia Arianne Panini do Carmo Luciane Regina Cavalli Luiz Fernando Bleggi Torres Andrea Senff Ribeiro Lucia de Noronha Cleber Machado-Souza Polymorphisms in Pathways in Pediatric Astrocytomas ASN Neuro |
| title | Polymorphisms in Pathways in Pediatric Astrocytomas |
| title_full | Polymorphisms in Pathways in Pediatric Astrocytomas |
| title_fullStr | Polymorphisms in Pathways in Pediatric Astrocytomas |
| title_full_unstemmed | Polymorphisms in Pathways in Pediatric Astrocytomas |
| title_short | Polymorphisms in Pathways in Pediatric Astrocytomas |
| title_sort | polymorphisms in pathways in pediatric astrocytomas |
| url | https://doi.org/10.1177/17590914231153481 |
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