Reproducibility of the NanoString 22-gene molecular subgroup assay for improved prognostic prediction of medulloblastoma

Detalhes bibliográficos
Autor(a) principal: Leal, Letícia F.
Data de Publicação: 2018
Outros Autores: 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.
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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spelling 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)
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