Single nCounter assay for prediction of MYCN amplification and molecular classification of medulloblastomas: a multicentric study

Purpose Medulloblastoma is the most frequent pediatric malignant brain tumor, and is divided into four main subgroups: WNT, SHH, group 3, and group 4. MYCN amplification is an important medulloblastoma prognostic biomarker. We aimed to molecular classify and predict MYCN amplification in a single as...

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Veröffentlicht in:Journal of neuro-oncology 2022-03, Vol.157 (1), p.27-35
Hauptverfasser: Moreno, Daniel Antunes, da Silva, Luciane Sussuchi, Zanon, Maicon Fernando, Bonatelli, Murilo, de Paula, Flávia Escremim, de Medeiros Matsushita, Marcus, Teixeira, Gustavo Ramos, Santana, Iara Viana Vidigal, Saggioro, Fabiano, Neder, Luciano, Stavale, João N., Malheiros, Suzana Maria Fleury, Lima, Matheus, Hajj, Glaucia Noeli Maroso, Garcia-Rivello, Hernan, Christiansen, Silvia, Nunes, Susana, da Costa, Maria João Gil, Soares, Maria José, Pinheiro, Jorge, Junior, Carlos Almeida, Mançano, Bruna Minniti, Reis, Rui Manuel
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container_end_page 35
container_issue 1
container_start_page 27
container_title Journal of neuro-oncology
container_volume 157
creator Moreno, Daniel Antunes
da Silva, Luciane Sussuchi
Zanon, Maicon Fernando
Bonatelli, Murilo
de Paula, Flávia Escremim
de Medeiros Matsushita, Marcus
Teixeira, Gustavo Ramos
Santana, Iara Viana Vidigal
Saggioro, Fabiano
Neder, Luciano
Stavale, João N.
Malheiros, Suzana Maria Fleury
Lima, Matheus
Hajj, Glaucia Noeli Maroso
Garcia-Rivello, Hernan
Christiansen, Silvia
Nunes, Susana
da Costa, Maria João Gil
Soares, Maria José
Pinheiro, Jorge
Junior, Carlos Almeida
Mançano, Bruna Minniti
Reis, Rui Manuel
description Purpose Medulloblastoma is the most frequent pediatric malignant brain tumor, and is divided into four main subgroups: WNT, SHH, group 3, and group 4. MYCN amplification is an important medulloblastoma prognostic biomarker. We aimed to molecular classify and predict MYCN amplification in a single assay. Methods It was included 209 medulloblastomas from 205 patients (Brazil, Argentina, and Portugal), divided into training ( n  = 50) and validation ( n  = 159) sets. A nCounter assay was carried out using a custom panel for molecular classification, with additional genes, including MYCN . nSolver 4.0 software and the R environment were used for profiling and MYCN mRNA analysis. MYCN amplification by FISH was performed in 64 cases. Results The 205 medulloblastomas were classified in SHH (44.9%), WNT (15.6%), group 3 (18.1%) and group 4 (21.4%). In the training set, MYCN amplification was detected in three SHH medulloblastomas by FISH, which showed significantly higher MYCN mRNA counts than non-FISH amplified cases, and a cutoff for MYCN amplification was established ( X ¯ + 4σ = 11,124.3). Applying this threshold value in the validation set, we identified MYCN mRNA counts above the cutoff in three cases, which were FISH validated. Conclusion We successfully stratified medulloblastoma molecular subgroups and predicted MYCN amplification using a single nCounter assay without the requirement of additional biological tissue, costs, or bench time.
doi_str_mv 10.1007/s11060-022-03965-1
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MYCN amplification is an important medulloblastoma prognostic biomarker. We aimed to molecular classify and predict MYCN amplification in a single assay. Methods It was included 209 medulloblastomas from 205 patients (Brazil, Argentina, and Portugal), divided into training ( n  = 50) and validation ( n  = 159) sets. A nCounter assay was carried out using a custom panel for molecular classification, with additional genes, including MYCN . nSolver 4.0 software and the R environment were used for profiling and MYCN mRNA analysis. MYCN amplification by FISH was performed in 64 cases. Results The 205 medulloblastomas were classified in SHH (44.9%), WNT (15.6%), group 3 (18.1%) and group 4 (21.4%). In the training set, MYCN amplification was detected in three SHH medulloblastomas by FISH, which showed significantly higher MYCN mRNA counts than non-FISH amplified cases, and a cutoff for MYCN amplification was established ( X ¯ + 4σ = 11,124.3). Applying this threshold value in the validation set, we identified MYCN mRNA counts above the cutoff in three cases, which were FISH validated. Conclusion We successfully stratified medulloblastoma molecular subgroups and predicted MYCN amplification using a single nCounter assay without the requirement of additional biological tissue, costs, or bench time.</description><identifier>ISSN: 0167-594X</identifier><identifier>EISSN: 1573-7373</identifier><identifier>DOI: 10.1007/s11060-022-03965-1</identifier><identifier>PMID: 35166989</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Brain cancer ; Brain tumors ; Cell cycle ; Classification ; Dehydrogenases ; Gene amplification ; Gene expression ; Genetic engineering ; Health sciences ; Hospitals ; Hybridization ; Laboratories ; Laboratory Investigation ; Medicine ; Medicine &amp; Public Health ; Medulloblastoma ; mRNA ; Neurology ; Oncology ; Pathology ; Pediatrics ; Wnt protein</subject><ispartof>Journal of neuro-oncology, 2022-03, Vol.157 (1), p.27-35</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022</rights><rights>2022. 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MYCN amplification is an important medulloblastoma prognostic biomarker. We aimed to molecular classify and predict MYCN amplification in a single assay. Methods It was included 209 medulloblastomas from 205 patients (Brazil, Argentina, and Portugal), divided into training ( n  = 50) and validation ( n  = 159) sets. A nCounter assay was carried out using a custom panel for molecular classification, with additional genes, including MYCN . nSolver 4.0 software and the R environment were used for profiling and MYCN mRNA analysis. MYCN amplification by FISH was performed in 64 cases. Results The 205 medulloblastomas were classified in SHH (44.9%), WNT (15.6%), group 3 (18.1%) and group 4 (21.4%). In the training set, MYCN amplification was detected in three SHH medulloblastomas by FISH, which showed significantly higher MYCN mRNA counts than non-FISH amplified cases, and a cutoff for MYCN amplification was established ( X ¯ + 4σ = 11,124.3). Applying this threshold value in the validation set, we identified MYCN mRNA counts above the cutoff in three cases, which were FISH validated. 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da Silva, Luciane Sussuchi ; Zanon, Maicon Fernando ; Bonatelli, Murilo ; de Paula, Flávia Escremim ; de Medeiros Matsushita, Marcus ; Teixeira, Gustavo Ramos ; Santana, Iara Viana Vidigal ; Saggioro, Fabiano ; Neder, Luciano ; Stavale, João N. ; Malheiros, Suzana Maria Fleury ; Lima, Matheus ; Hajj, Glaucia Noeli Maroso ; Garcia-Rivello, Hernan ; Christiansen, Silvia ; Nunes, Susana ; da Costa, Maria João Gil ; Soares, Maria José ; Pinheiro, Jorge ; Junior, Carlos Almeida ; Mançano, Bruna Minniti ; Reis, Rui Manuel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c424t-8388a1d9d9e7c6dc034405e618086fdbd1fa8cf0759dd2cb9ef86f757a980df53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Brain cancer</topic><topic>Brain tumors</topic><topic>Cell cycle</topic><topic>Classification</topic><topic>Dehydrogenases</topic><topic>Gene amplification</topic><topic>Gene expression</topic><topic>Genetic engineering</topic><topic>Health sciences</topic><topic>Hospitals</topic><topic>Hybridization</topic><topic>Laboratories</topic><topic>Laboratory Investigation</topic><topic>Medicine</topic><topic>Medicine &amp; 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MYCN amplification is an important medulloblastoma prognostic biomarker. We aimed to molecular classify and predict MYCN amplification in a single assay. Methods It was included 209 medulloblastomas from 205 patients (Brazil, Argentina, and Portugal), divided into training ( n  = 50) and validation ( n  = 159) sets. A nCounter assay was carried out using a custom panel for molecular classification, with additional genes, including MYCN . nSolver 4.0 software and the R environment were used for profiling and MYCN mRNA analysis. MYCN amplification by FISH was performed in 64 cases. Results The 205 medulloblastomas were classified in SHH (44.9%), WNT (15.6%), group 3 (18.1%) and group 4 (21.4%). In the training set, MYCN amplification was detected in three SHH medulloblastomas by FISH, which showed significantly higher MYCN mRNA counts than non-FISH amplified cases, and a cutoff for MYCN amplification was established ( X ¯ + 4σ = 11,124.3). Applying this threshold value in the validation set, we identified MYCN mRNA counts above the cutoff in three cases, which were FISH validated. Conclusion We successfully stratified medulloblastoma molecular subgroups and predicted MYCN amplification using a single nCounter assay without the requirement of additional biological tissue, costs, or bench time.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>35166989</pmid><doi>10.1007/s11060-022-03965-1</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-9639-7940</orcidid></addata></record>
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subjects Brain cancer
Brain tumors
Cell cycle
Classification
Dehydrogenases
Gene amplification
Gene expression
Genetic engineering
Health sciences
Hospitals
Hybridization
Laboratories
Laboratory Investigation
Medicine
Medicine & Public Health
Medulloblastoma
mRNA
Neurology
Oncology
Pathology
Pediatrics
Wnt protein
title Single nCounter assay for prediction of MYCN amplification and molecular classification of medulloblastomas: a multicentric study
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