Medulloblastoma subgroups remain stable across primary and metastatic compartments.
Medulloblastoma subgroups remain stable across primary and metastatic compartments.
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DOI：
10.1007/s00401-015-1389-0
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发表时间：
2015-03
影响因子：
12.7
通讯作者：
Taylor MD
中科院分区：
文献类型：
--
作者：
Wang X;Dubuc AM;Ramaswamy V;Mack S;Gendoo DM;Remke M;Wu X;Garzia L;Luu B;Cavalli F;Peacock J;López B;Skowron P;Zagzag D;Lyden D;Hoffman C;Cho YJ;Eberhart C;MacDonald T;Li XN;Van Meter T;Northcott PA;Haibe-Kains B;Hawkins C;Rutka JT;Bouffet E;Pfister SM;Korshunov A;Taylor MD
髓母细胞瘤包括四种不同的分子变异，具有不同的遗传学，转录组和结果。亚组隶属关系先前已被证明在复发时保持稳定，这可能反映了它们不同的起源细胞。然而，一个治疗相关的问题，仍然没有答案是亚组的稳定性转移区室。我们在MAGIC联盟中收集了12对原发性转移性肿瘤，并通过整合基因表达和DNA甲基化分析建立了它们的分子亚组关系。收集冷冻组织，并使用Affyrin基因表达阵列和Illumina甲基化阵列进行分析。类预测和层次聚类使用现有的已发表的数据集进行。我们的分子分析，使用一致的整合基因组数据，建立了明确的维护分子亚群的联系，在转移性髓母细胞瘤。我们进一步验证了这些发现，通过询问一个非重叠的队列的19对原发性转移性肿瘤从Burdenko神经外科研究所使用正交技术的免疫组织化学染色。这项研究代表了迄今为止报告的最大的原发性-转移性配对队列，并提供了一个独特的机会来评价转移区室中亚组特异性分子畸变。我们的研究结果进一步支持了髓母细胞瘤亚群起源于不同细胞的假设，这些细胞是从个体发育到肿瘤学的。
Medulloblastoma comprises four distinct molecular variants with distinct genetics, transcriptomes, and outcomes. Subgroup affiliation has been previously shown to remain stable at the time of recurrence, which likely reflects their distinct cells of origin. However, a therapeutically relevant question that remains unanswered is subgroup stability in the metastatic compartment. We assembled a cohort of 12-paired primary-metastatic tumors collected in the MAGIC consortium, and established their molecular subgroup affiliation by performing integrative gene expression and DNA methylation analysis. Frozen tissues were collected and profiled using Affymetrix gene expression arrays and Illumina methylation arrays. Class prediction and hierarchical clustering were performed using existing published datasets. Our molecular analysis, using consensus integrative genomic data, establishes the unequivocal maintenance of molecular subgroup affiliation in metastatic medulloblastoma. We further validated these findings by interrogating a non-overlapping cohort of 19-pairs of primary-metastatic tumors from the Burdenko Neurosurgical Institute using an orthogonal technique of immunohistochemical staining. This investigation represents the largest reported primary-metastatic paired cohort profiled to date and provides a unique opportunity to evaluate subgroup-specific molecular aberrations within the metastatic compartment. Our findings further support the hypothesis that medulloblastoma subgroups arise from distinct cells of origin, which are carried forward from ontogeny to oncology.
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影响因子：
45.3
作者：
Remke, Marc;Hielscher, Thomas;Korshunov, Andrey
通讯作者：
Korshunov, Andrey
影响因子：
15.9
作者：
Dolecek, Therese A.;Propp, Jennifer M.;Kruchko, Carol
通讯作者：
Kruchko, Carol
影响因子：
45.3
作者：
Gandola, Lorenza;Massimino, Maura;Fossati-Bellani, Franca
通讯作者：
Fossati-Bellani, Franca
影响因子：
45.3
作者：
Thompson, MC;Fuller, C;Gilbertson, RJ
通讯作者：
Gilbertson, RJ
影响因子：
12.7
作者：
Taylor MD;Northcott PA;Korshunov A;Remke M;Cho YJ;Clifford SC;Eberhart CG;Parsons DW;Rutkowski S;Gajjar A;Ellison DW;Lichter P;Gilbertson RJ;Pomeroy SL;Kool M;Pfister SM
通讯作者：
Pfister SM