PO.CL06.02 · 临床研究
Beat Childhood Cancer研究联盟中的综合性儿童生物样本库建设与模型开发
Comprehensive pediatric biobanking and model development in the Beat Childhood Cancer Research Consortium
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
宾夕法尼亚州立大学（PSU）的儿童肿瘤转化研究实验室（POTRL）提供了一个关键的、集中化的、经LIMS追踪的储存库，收藏超过70,000份儿童癌症标本和患者来源模型，通过Beat Childhood Cancer（BCC）研究联盟为精准肿瘤学领域的创新性转化研究提供经验证的资源。
背景：
可靠的转化研究依赖于高质量、经充分表征的患者材料。BCC运营一个通过PSU的POTRL管理的集中化储存库。POTRL接收、处理并存储来自多项BCC临床试验的生物标本，代表患有神经母细胞瘤、中枢神经系统（CNS）肿瘤、肉瘤及其他实体恶性肿瘤的儿童。该储存库包括肿瘤组织、组织切片、石蜡包埋块，以及经处理用于ctDNA、血沉棕黄层、免疫细胞、细胞因子和生物标志物分析的血液/血浆。
方法：
所有标本均在Freezerworks LIMS中登记并追踪，以确保准确的标记和存储。患者签署BCC-BIO-001研究（NCT04715178）的知情同意，该研究收集肿瘤的全外显子和全转录组测序、患者的临床诊断、病理、治疗和结局。样本接收后即检查其完整性和温度合规性。从肿瘤组织及骨芯/穿刺物中生成细胞系、类器官和异种移植物，各自在IDEXX BioAnalytics通过短串联重复（STR）分型进行认证，并同步进行支原体检测和匹配的患者参照。肿瘤系验证通过流式细胞术分析进行，使用肿瘤特异性标志物组合，如尤因肉瘤（CD99）；神经母细胞瘤（GD2、CD56、Synaptophysin）；或髓母细胞瘤（CD56、Synaptophysin）。
结果：
该储存库目前收藏来自5,000余名儿童患者的70,000余份标本。已建立超过750个患者来源细胞系和150个患者来源异种移植（PDX）模型。基于LIMS的追踪的实施改善了标本组织和数据一致性，使得能够追踪连续的患者样本。每份样本均与存储于REDCap数据库中的治疗和结局时间点相关联。患者来源类器官模型的开发近期已经启动，并在多种肿瘤类型中持续进行，维持着与原发肿瘤一致的标志物特征。
结论：
POTRL为儿童癌症标本的收集、验证和模型生成提供了一个整合的平台。这些经充分表征的资源支持宾夕法尼亚州立大学的转化研究项目，并在全国和国际范围内的BCC研究中心间共享，以加速儿童癌症的生物标志物发现、临床前测试和精准肿瘤学研究。
查看英文原文 English abstract
The Pediatric Oncology Translational Research Lab (POTRL) at Penn State University (PSU) provides a critical centralized, LIMS-tracked repository of over 70,000 pediatric cancer specimens and patient-derived models, enabling validated resources for innovative translational research in precision-oncology through the Beat Childhood Cancer (BCC) Research Consortium.
Background:
Reliable translational research depends on high quality, well characterized patient materials. BCC operates a centralized repository managed through the POTRL at PSU. POTRL receives, processes, and stores biospecimens from multiple BCC clinical trials representing children with neuroblastoma, CNS tumors, sarcomas, and other solid malignancies. The repository includes tumor tissue, tissue slides, paraffin-embedded blocks, and blood/plasma that are processed for ctDNA, buffy coats, immune cells, cytokines, and biomarker analyses.
Methods:
All specimens are accessioned and tracked in Freezerworks LIMS to ensure accurate labeling and storage. Patients are consented to the BCC-BIO-001 study (NCT04715178) which collects whole exome and whole transcriptome sequencing of tumors, clinical diagnosis, pathology, treatment and outcomes of patients. Upon receipt, samples are inspected for integrity and temperature compliance. Cell lines, organoids and xenografts are generated from tumor tissue and bone cores/aspirates each of which undergo authentication at IDEXX BioAnalytics using short tandem repeat profiling with concurrent mycoplasma testing and matched patient references. Tumor line validation is performed by flow cytometric analysis using tumor-specific marker panels such as Ewings sarcoma (CD99); neuroblastoma (GD2, CD56, Synaptophysin); or medulloblastoma (CD56, Synaptophysin).
Results:
The repository currently houses more than 70,000 specimens from over 5,000 pediatric patients. Over 750 patient-derived cell lines and 150 patient-derived xenograft models have been established. Implementation of LIMS-based tracking has improved specimen organization and data consistency allowing for tracking of sequential patient samples. Each sample is correlated to timepoints in treatments and outcomes stored in the REDCap database. Development of patient-derived organoid models has recently begun and is ongoing across multiple tumor types, maintaining marker profiles consistent with primary tumors.
Conclusions:
POTRL provides an integrated platform for the collection, validation, and model generation of pediatric cancer specimens. These well characterized resources support translational research projects at Penn State and are shared throughout the BCC research centers nationally and internationally to accelerate biomarker discovery, preclinical testing, and precision-oncology studies for pediatric cancers.
利益披露 Disclosure
D. Gandra, None..
K. McClain, None..
M. Shukla, None..
L. Vazquez, None..
M. Haque, None..
J. Lerch, None..
M. Younis, None..
T. Walter Angelo, None..
J. Hengst, None..
G. S. Sholler, None.