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000143213 1001_ $$00000-0002-0005-3984$$aCruzeiro, Gustavo Alencastro Veiga$$b0
000143213 245__ $$aA simplified approach using Taqman low-density array for medulloblastoma subgrouping.
000143213 260__ $$aLondon$$bBiomed Central$$c2019
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000143213 520__ $$aNext-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 450 K to assess methylation profile along with 390 MB 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 450 k. Similarly, we tested this simplified set of gene signatures in 763 MB samples and we were 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.
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000143213 7001_ $$aSalomão, Karina Bezerra$$b1
000143213 7001_ $$ade Biagi, Carlos Alberto Oliveira$$b2
000143213 7001_ $$aBaumgartner, Martin$$b3
000143213 7001_ $$0P:(DE-He78)a46a5b2a871859c8e2d63d2f8c666807$$aSturm, Dominik$$b4$$udkfz
000143213 7001_ $$aLira, Régia Caroline Peixoto$$b5
000143213 7001_ $$ade Almeida Magalhães, Taciani$$b6
000143213 7001_ $$aBaroni Milan, Mirella$$b7
000143213 7001_ $$ada Silva Silveira, Vanessa$$b8
000143213 7001_ $$aSaggioro, Fabiano Pinto$$b9
000143213 7001_ $$ade Oliveira, Ricardo Santos$$b10
000143213 7001_ $$aDos Santos Klinger, Paulo Henrique$$b11
000143213 7001_ $$aSeidinger, Ana Luiza$$b12
000143213 7001_ $$aYunes, José Andrés$$b13
000143213 7001_ $$ade Paula Queiroz, Rosane Gomes$$b14
000143213 7001_ $$aOba-Shinjo, Sueli Mieko$$b15
000143213 7001_ $$aScrideli, Carlos Alberto$$b16
000143213 7001_ $$aNagahashi, Suely Marie Kazue$$b17
000143213 7001_ $$aTone, Luiz Gonzaga$$b18
000143213 7001_ $$aValera, Elvis Terci$$b19
000143213 773__ $$0PERI:(DE-600)2715589-4$$a10.1186/s40478-019-0681-y$$gVol. 7, no. 1, p. 33$$n1$$p33$$tActa Neuropathologica Communications$$v7$$x2051-5960$$y2019
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000143213 9141_ $$y2019
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