Expression of GNAS, TP53, and PTEN Improves the Patient Prognostication in Sonic Hedgehog (SHH) Medulloblastoma Subgroup
| Autor: | Glaucia N. M. Hajj, Gisele Caravina de Almeida, Rui Manuel Reis, Leticia Ferro Leal, Suzana M. F. Malheiros, Marcos Alves de Lima, Marcus Matsushita, Luciane Sussuchi da Silva, Mariana Bisarro dos Reis, Luciano Neder Serafini, João Norberto Stávale, Matheus Lima, Adriane Feijó Evangelista, Fabiano Pinto Saggioro, Flavia de Paula, Bruna Minniti Mançano, Michael D. Taylor, Carlos Roberto Almeida Junior |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Oncology medicine.medical_specialty Adolescent DNA Mutational Analysis Malignant brain tumor Pathology and Forensic Medicine Cohort Studies Young Adult 03 medical and health sciences 0302 clinical medicine Molecular classification SOX2 Internal medicine Chromogranins GTP-Binding Protein alpha Subunits Gs medicine GNAS complex locus Humans PTEN Hedgehog Proteins Sonic hedgehog Cerebellar Neoplasms Child neoplasms Gene Medulloblastoma biology business.industry PTEN Phosphohydrolase High-Throughput Nucleotide Sequencing Infant Prognosis medicine.disease 030104 developmental biology Child Preschool 030220 oncology & carcinogenesis Mutation biology.protein Molecular Medicine Female Tumor Suppressor Protein p53 Transcriptome business Brazil |
| Zdroj: | The Journal of Molecular Diagnostics. 22:957-966 |
| ISSN: | 1525-1578 |
| DOI: | 10.1016/j.jmoldx.2020.04.207 |
| Popis: | Medulloblastoma (MB) is the most common malignant brain tumor in children. It is currently classified in four main molecular subgroups with different clinical outcomes: sonic hedgehog, wingless, group 3, and group 4 (MBSHH, MBWNT, MBGRP3, or MBGRP4). Presently, a 22-gene expression panel has been efficiently applied for molecular subgrouping using nCounter technology. In this study, formalin-fixed, paraffin-embedded samples from 164 Brazilian medulloblastomas were evaluated, applying the 22-gene panel, and subclassified into the low and high expression of nine key medulloblastoma-related genes. In addition, TP53 mutation status was assessed using TruSight Tumor 15 Panel, and its correlation with expression and prognostic impact was evaluated. Samples from 149 of 164 patients (90%) were classified into MBSHH (47.7%), MBWNT (16.1%), MBGRP3 (15.4%), and MBGRP4 (20.8%). GNAS presented the highest expression levels, with higher expression in MBSHH. TP53, MYCN, SOX2, and MET were also up-regulated in MBSHH, whereas PTEN was up-regulated in MBGRP4. GNAS, TP53, and PTEN low expression was associated with the unfavorable patient outcome only for MBSHH (P = 0.04, P = 0.01, and P = 0.02, respectively). TP53 mutations were detected in 28.57% of MBSHH cases and exhibited association with lower expression and worse clinical outcome, although not statistically significant. The 22-gene panel for molecular classification of medulloblastoma associated with the expression of GNAS, TP53, and PTEN improves the patient prognostication in MBSHH subgroup and can be easily incorporated in the 22-gene panel without any additional costs. |
| Databáze: | OpenAIRE |
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