当前位置: X-MOL 学术Nat. Med. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
A biobank of patient-derived pediatric brain tumor models.
Nature Medicine ( IF 82.9 ) Pub Date : 2018-Nov-01 , DOI: 10.1038/s41591-018-0207-3
Sebastian Brabetz , Sarah E. S. Leary , Susanne N. Gröbner , Madison W. Nakamoto , Huriye Şeker-Cin , Emily J. Girard , Bonnie Cole , Andrew D. Strand , Karina L. Bloom , Volker Hovestadt , Norman L. Mack , Fiona Pakiam , Benjamin Schwalm , Andrey Korshunov , Gnana Prakash Balasubramanian , Paul A. Northcott , Kyle D. Pedro , Joyoti Dey , Stacey Hansen , Sally Ditzler , Peter Lichter , Lukas Chavez , David T. W. Jones , Jan Koster , Stefan M. Pfister , Marcel Kool , James M. Olson

Brain tumors are the leading cause of cancer-related death in children. Genomic studies have provided insights into molecular subgroups and oncogenic drivers of pediatric brain tumors that may lead to novel therapeutic strategies. To evaluate new treatments, better preclinical models adequately reflecting the biological heterogeneity are needed. Through the Children's Oncology Group ACNS02B3 study, we have generated and comprehensively characterized 30 patient-derived orthotopic xenograft models and seven cell lines representing 14 molecular subgroups of pediatric brain tumors. Patient-derived orthotopic xenograft models were found to be representative of the human tumors they were derived from in terms of histology, immunohistochemistry, gene expression, DNA methylation, copy number, and mutational profiles. In vivo drug sensitivity of targeted therapeutics was associated with distinct molecular tumor subgroups and specific genetic alterations. These models and their molecular characterization provide an unprecedented resource for the cancer community to study key oncogenic drivers and to evaluate novel treatment strategies.

中文翻译:

患者来源的小儿脑肿瘤模型的生物库。

脑肿瘤是儿童癌症相关死亡的主要原因。基因组学研究提供了小儿脑肿瘤的分子亚群和致癌驱动因素的见识,这可能会导致新的治疗策略。为了评估新的治疗方法,需要能够更好地反映生物学异质性的更好的临床前模型。通过儿童肿瘤学组ACNS02B3的研究,我们已经生成并全面表征了30种患者源性原位异种移植模型和7种细胞系,它们代表了小儿脑肿瘤的14个分子亚群。在组织学,免疫组织化学,基因表达,DNA甲基化,拷贝数和突变谱方面,发现患者来源的原位异种移植模型代表了人类肿瘤的代表。靶向治疗药物的体内药物敏感性与不同的分子肿瘤亚组和特定的遗传改变有关。这些模型及其分子表征为癌症界提供了前所未有的资源,以研究关键的致癌驱动因素并评估新颖的治疗策略。
更新日期:2018-10-23
down
wechat
bug