A simplified approach using Taqman low-density array for medulloblastoma subgrouping

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art_CRUZEIRO_A_simplified_approach_using_Taqman_lowdensity_array_for_2019.PDF (3.9 MB)
Citações na Scopus
18
Tipo de produção
article
Data de publicação
2019
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
BMC
Autores
CRUZEIRO, Gustavo Alencastro Veiga
SALOMAO, Karina Bezerra
BIAGI JR., Carlos Alberto Oliveira de
BAUMGARTNER, Martin
STURM, Dominik
LIRA, Regia Caroline Peixoto
MAGALHAES, Taciani de Almeida
MILAN, Mirella Baroni
SILVEIRA, Vanessa da Silva
SAGGIORO, Fabiano Pinto
Citação
ACTA NEUROPATHOLOGICA COMMUNICATIONS, v.7, article ID 33, 10p, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Next-generation sequencing platforms are routinely used for molecular assignment due to their high impact for risk stratification and prognosis in medulloblastomas. Yet, low and middle-income countries still lack an accurate cost-effective platform to perform this allocation. TaqMan Low Density array (TLDA) assay was performed using a set of 20 genes in 92 medulloblastoma samples. The same methodology was assessed in silico using microarray data for 763 medulloblastoma samples from the GSE85217 study, which performed MB classification by a robust integrative method (Transcriptional, Methylation and cytogenetic profile). Furthermore, we validated in 11 MBs samples our proposed method by Methylation Array 450K to assess methylation profile along with 390MB samples (GSE109381) and copy number variations. TLDA with only 20 genes accurately assigned MB samples into WNT, SHH, Group 3 and Group 4 using Pearson distance with the average-linkage algorithm and showed concordance with molecular assignment provided by Methylation Array 450k. Similarly, we tested this simplified set of gene signatures in 763MB samples and wewere able to recapitulate molecular assignment with an accuracy of 99.1% (SHH), 94.29% (WNT), 92.36% (Group 3) and 95.40% (Group 4), against 97.31, 97.14, 88.89 and 97.24% (respectively) with the Ward.D2 algorithm. t-SNE analysis revealed a high level of concordance (k=4) with minor overlapping features between Group 3 and Group 4. Finally, we condensed the number of genes to 6 without significantly losing accuracy in classifying samples into SHH, WNT and non-SHH/non-WNT subgroups. Additionally, we found a relatively high frequency of WNT subgroup in our cohort, which requires further epidemiological studies. TLDA is a rapid, simple and cost-effective assay for classifying MB in low/middle income countries. A simplified method using six genes and restricting the final stratification into SHH, WNT and non-SHH/non-WNT appears to be a very interesting approach for rapid clinical decision-making.
Palavras-chave
Medulloblastoma, Molecular subgroups, Brazilian cohort, Real-time PCR
URI
https://observatorio.fm.usp.br/handle/OPI/31730
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MNE
Artigos e Materiais de Revistas Científicas - LIM/15