Cross-site Concordance Evaluation of Tumor DNA and RNA Sequencing Platforms of CIMAC-CIDC Network

The Cancer Immune Monitoring and Analysis Centers (CIMACs) and the Cancer Immunologic Data Commons (CIDC)  has engaged in efforts to harmonize Whole-exome (WES) and RNA-sequencing (RNA-seq) data from three different experimental platforms (MD Anderson, NCI MoCha lab, and Broad Institute) and are using a series of developed pipelines to process the early trial samples. To evaluate the consistency of tumor WES and RNA-seq profiling platforms across different centers, the CIMACs-CIDC conducted a systematic harmonization study. DNA and RNA were centrally extracted from fresh frozen (FF) and formalin-fixed paraffin-embedded (FFPE) non-small cell lung carcinoma (NSCLC) tumors and distributed to three centers for WES and RNA-seq profiling]]>
Matched formalin-fixed paraffin-embedded (FFPE) tumor, fresh frozen (FF) tumor, and peripheral blood mononuclear cells (PBMC) from eight patients with NSCLC of squamous cell carcinoma histology were studied. Inclusion criteria: Tumors  collected between the years 2012 and 2015. Exclusion criteria: Patients without matching FFPE, FF, and PBMC samples ]]>
To enhance the value of correlative studies for the next level of success in CIMACs-CIDC network, a robust and coordinated biomarker strategy across trials and organizations is needed.  Elements critical to such efforts including capacity for deep tumor and immune profiling and analysis, assay platforms that are not only analytically validated and fit for purpose, and standardized or harmonization between labs need to bee evaluated. To address these challenges, the NCI and industry are collaborating on a systematic cross-sector approach to biomarker assay development, validation, and standardization. To conduct highly-specialized and uniformly-performed biomarker testing in a wide range of immunotherapy trials, CIMACs-CIDC works to provide a data repository and informatics platform for integration of clinical and biomarker data from correlative analyses. To achieve these goals, the CIMAC-CIDC engaged in a wide range of well validated and harmonized across different sited assays platforms to conduct bioassays and analysis on biospecimens from clinical trials that are selected from both NCI- and externally-sponsored trial organizations ]]>

癌症免疫监测与分析中心（CIMACs）与癌症免疫数据共享平台（CIDC）已开展工作，对来自三个不同实验平台（安德森癌症中心（MD Anderson）、NCI MoCha实验室以及博德研究所（Broad Institute））的全外显子测序（WES）与RNA测序（RNA-seq）数据进行标准化整合，并通过一系列自研分析流程处理早期临床试验样本。为评估不同中心的肿瘤WES与RNA-seq测序分析平台的一致性，CIMACs-CIDC开展了一项系统性标准化整合研究。研究人员从新鲜冷冻（FF）及福尔马林固定石蜡包埋（FFPE）的非小细胞肺癌（NSCLC）肿瘤样本中统一提取DNA与RNA，并将样本分发至三个中心进行WES与RNA-seq测序分析。

本研究纳入8例鳞状组织学类型非小细胞肺癌患者的配对样本，包括福尔马林固定石蜡包埋（FFPE）肿瘤组织、新鲜冷冻（FF）肿瘤组织以及外周血单个核细胞（PBMC）。纳入标准：样本采集于2012年至2015年间。排除标准：无法提供匹配的FFPE、FF及PBMC样本的患者。

为提升CIMACs-CIDC网络中关联研究的价值以实现更高层级的研究成果，亟需建立一套跨试验与跨机构的稳健且协同的生物标志物研究策略。此类工作的关键要素包括：深度肿瘤与免疫组学分析能力、经分析验证且符合应用需求的检测平台，以及实验室间的标准化与整合流程，均需得到评估。为应对上述挑战，美国国家癌症研究所（NCI）与产业界正合作开展系统性跨领域工作，以推进生物标志物检测的开发、验证与标准化。为在大量免疫治疗临床试验中开展高度专业化且操作统一的生物标志物检测，CIMACs-CIDC致力于搭建数据存储库与信息学平台，以整合相关分析中的临床数据与生物标志物数据。为达成上述目标，CIMAC-CIDC已采用一系列经充分验证且跨站点标准化的检测平台，对来自NCI赞助及外部赞助的临床试验的生物样本开展生物检测与分析工作。