Reproducibility of the NanoString 22-gene molecular subgroup assay for improved prognostic prediction of medulloblastoma
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/1822/57968 |
Resumo: | Medulloblastoma is the most frequent malignant brain tumor in children. Four medulloblastoma molecular subgroups, MBSHH , MBWNT , MBGRP3 and MBGRP4 , have been identified by integrated high-throughput platforms. Recently, a 22-gene panel NanoString-based assay was developed for medulloblastoma molecular subgrouping, but the robustness of this assay has not been widely evaluated. Mutations in the gene for human telomerase reverse transcriptase (hTERT) have been found in medulloblastomas and are associated with distinct molecular subtypes. This study aimed to implement the 22-gene panel in a Brazilian context, and to associate the molecular profile with patients' clinical-pathological features. Formalin-fixed, paraffin-embedded (FFPE) medulloblastoma samples (n = 104) from three Brazilian centers were evaluated. Expression profiling of the 22-gene panel was performed by NanoString and a Canadian series (n = 240) was applied for training phase. hTERT mutations were analyzed by PCR followed by direct Sanger sequencing and the molecular profile was associated with patients' clinicopathological features. Overall, 65% of the patients were male, average age at diagnosis was 18 years and 7% of the patients presented metastasis at diagnosis. The molecular classification was attained in 100% of the cases, with the following frequencies: MBSHH (n = 51), MBWNT (n = 19), MBGRP4 (n = 19) and MBGRP3 (n = 15). The MBSHH and MBGRP3 subgroups were associated with older and younger patients, respectively. The MBGRP4 subgroup exhibited the lowest 5-year cancer-specific overall survival (OS), yet in the multivariate analysis, only metastasis at diagnosis and surgical resection were associated with OS. hTERT mutations were detected in 29% of the cases and were associated with older patients, increased hTERT expression and MBSHH subgroup. The 22-gene panel provides a reproducible assay for molecular subgrouping of medulloblastoma FFPE samples in a routine setting and is well-suited for future clinical trials. |
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Reproducibility of the NanoString 22-gene molecular subgroup assay for improved prognostic prediction of medulloblastomahTERTMedulloblastomaMolecular subgroupsNanoStringScience & TechnologyMedulloblastoma is the most frequent malignant brain tumor in children. Four medulloblastoma molecular subgroups, MBSHH , MBWNT , MBGRP3 and MBGRP4 , have been identified by integrated high-throughput platforms. Recently, a 22-gene panel NanoString-based assay was developed for medulloblastoma molecular subgrouping, but the robustness of this assay has not been widely evaluated. Mutations in the gene for human telomerase reverse transcriptase (hTERT) have been found in medulloblastomas and are associated with distinct molecular subtypes. This study aimed to implement the 22-gene panel in a Brazilian context, and to associate the molecular profile with patients' clinical-pathological features. Formalin-fixed, paraffin-embedded (FFPE) medulloblastoma samples (n = 104) from three Brazilian centers were evaluated. Expression profiling of the 22-gene panel was performed by NanoString and a Canadian series (n = 240) was applied for training phase. hTERT mutations were analyzed by PCR followed by direct Sanger sequencing and the molecular profile was associated with patients' clinicopathological features. Overall, 65% of the patients were male, average age at diagnosis was 18 years and 7% of the patients presented metastasis at diagnosis. The molecular classification was attained in 100% of the cases, with the following frequencies: MBSHH (n = 51), MBWNT (n = 19), MBGRP4 (n = 19) and MBGRP3 (n = 15). The MBSHH and MBGRP3 subgroups were associated with older and younger patients, respectively. The MBGRP4 subgroup exhibited the lowest 5-year cancer-specific overall survival (OS), yet in the multivariate analysis, only metastasis at diagnosis and surgical resection were associated with OS. hTERT mutations were detected in 29% of the cases and were associated with older patients, increased hTERT expression and MBSHH subgroup. The 22-gene panel provides a reproducible assay for molecular subgrouping of medulloblastoma FFPE samples in a routine setting and is well-suited for future clinical trials.We thank Barretos Cancer Hospital and FINEP (MCTI/FINEP/MS/SCTIE/DECIT - BioPlat 1302/13) for partially funding the present study. LFL is supported by Public Ministry of Labor Campinas (Research, Prevention and Education of Occupational Cancer) in Campinas, Brazil. RMR is sponsored by National Council for Scientific and Technological Development (CNPq, Brazil).info:eu-repo/semantics/publishedVersionWiley[et al.]Universidade do MinhoLeal, Letícia F.Evangelista, Adriane F.Paula, Flávia E. deAlmeida, Gisele CaravinaCarloni, Adriana C.Saggioro, FabianoStavale, João N.Malheiros, Suzana M. F.Mançano, BrunaReis, R. M.2018-102018-10-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/57968eng0919-65441440-178910.1111/neup.1250830155928info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:47:28Zoai:repositorium.sdum.uminho.pt:1822/57968Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:45:34.547195Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Reproducibility of the NanoString 22-gene molecular subgroup assay for improved prognostic prediction of medulloblastoma |
title |
Reproducibility of the NanoString 22-gene molecular subgroup assay for improved prognostic prediction of medulloblastoma |
spellingShingle |
Reproducibility of the NanoString 22-gene molecular subgroup assay for improved prognostic prediction of medulloblastoma Leal, Letícia F. hTERT Medulloblastoma Molecular subgroups NanoString Science & Technology |
title_short |
Reproducibility of the NanoString 22-gene molecular subgroup assay for improved prognostic prediction of medulloblastoma |
title_full |
Reproducibility of the NanoString 22-gene molecular subgroup assay for improved prognostic prediction of medulloblastoma |
title_fullStr |
Reproducibility of the NanoString 22-gene molecular subgroup assay for improved prognostic prediction of medulloblastoma |
title_full_unstemmed |
Reproducibility of the NanoString 22-gene molecular subgroup assay for improved prognostic prediction of medulloblastoma |
title_sort |
Reproducibility of the NanoString 22-gene molecular subgroup assay for improved prognostic prediction of medulloblastoma |
author |
Leal, Letícia F. |
author_facet |
Leal, Letícia F. Evangelista, Adriane F. Paula, Flávia E. de Almeida, Gisele Caravina Carloni, Adriana C. Saggioro, Fabiano Stavale, João N. Malheiros, Suzana M. F. Mançano, Bruna Reis, R. M. |
author_role |
author |
author2 |
Evangelista, Adriane F. Paula, Flávia E. de Almeida, Gisele Caravina Carloni, Adriana C. Saggioro, Fabiano Stavale, João N. Malheiros, Suzana M. F. Mançano, Bruna Reis, R. M. |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
[et al.] Universidade do Minho |
dc.contributor.author.fl_str_mv |
Leal, Letícia F. Evangelista, Adriane F. Paula, Flávia E. de Almeida, Gisele Caravina Carloni, Adriana C. Saggioro, Fabiano Stavale, João N. Malheiros, Suzana M. F. Mançano, Bruna Reis, R. M. |
dc.subject.por.fl_str_mv |
hTERT Medulloblastoma Molecular subgroups NanoString Science & Technology |
topic |
hTERT Medulloblastoma Molecular subgroups NanoString Science & Technology |
description |
Medulloblastoma is the most frequent malignant brain tumor in children. Four medulloblastoma molecular subgroups, MBSHH , MBWNT , MBGRP3 and MBGRP4 , have been identified by integrated high-throughput platforms. Recently, a 22-gene panel NanoString-based assay was developed for medulloblastoma molecular subgrouping, but the robustness of this assay has not been widely evaluated. Mutations in the gene for human telomerase reverse transcriptase (hTERT) have been found in medulloblastomas and are associated with distinct molecular subtypes. This study aimed to implement the 22-gene panel in a Brazilian context, and to associate the molecular profile with patients' clinical-pathological features. Formalin-fixed, paraffin-embedded (FFPE) medulloblastoma samples (n = 104) from three Brazilian centers were evaluated. Expression profiling of the 22-gene panel was performed by NanoString and a Canadian series (n = 240) was applied for training phase. hTERT mutations were analyzed by PCR followed by direct Sanger sequencing and the molecular profile was associated with patients' clinicopathological features. Overall, 65% of the patients were male, average age at diagnosis was 18 years and 7% of the patients presented metastasis at diagnosis. The molecular classification was attained in 100% of the cases, with the following frequencies: MBSHH (n = 51), MBWNT (n = 19), MBGRP4 (n = 19) and MBGRP3 (n = 15). The MBSHH and MBGRP3 subgroups were associated with older and younger patients, respectively. The MBGRP4 subgroup exhibited the lowest 5-year cancer-specific overall survival (OS), yet in the multivariate analysis, only metastasis at diagnosis and surgical resection were associated with OS. hTERT mutations were detected in 29% of the cases and were associated with older patients, increased hTERT expression and MBSHH subgroup. The 22-gene panel provides a reproducible assay for molecular subgrouping of medulloblastoma FFPE samples in a routine setting and is well-suited for future clinical trials. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-10 2018-10-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://hdl.handle.net/1822/57968 |
url |
https://hdl.handle.net/1822/57968 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0919-6544 1440-1789 10.1111/neup.12508 30155928 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Wiley |
publisher.none.fl_str_mv |
Wiley |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799133021039755264 |