Central diagnostics, genomics and biobanking

需要深入研究具有特征的原发性患者材料，以发现CLL中具有重要生物学和临床相关性的关键驱动分子。因此，必须证明新发现依赖或独立于先前在CLL中建立的分子预后参数。为了给CRU-286的所有科学家提供定义明确的人类和小鼠原发性CLL细胞样本，中央诊断、基因组分析和生物银行将在这个核心项目2 （CP2）中进行。在病理学研究所（R. b<s:1> ttner）、科隆基因组学中心（P. n<e:1> rnberg）和内科（血液学/肿瘤学，k . a）建立了先进的免疫表型分型、虚拟显微镜、图像分析和存储平台以及先进的翻译基因组学的合作结构。Kreuzer， C. Schweighofer)。外周血、骨髓和包括淋巴结在内的组织标本将进行形态学诊断，并进行系统的诊断检查，包括免疫表型分析、体细胞突变分析（即TP53、IGHV）、荧光原位杂交和常规细胞遗传学。此外，适当的蛋白质和核酸提取物将在适当的数据保护和安全要求下集中存储。使用完全可操作的基因组学单元，按需全基因组，外显子组或目标富集基因提取物将通过平行转录组和单核苷酸变异（SNV）分析进行深度测序。在科隆大学医院(UHC)/综合肿瘤学中心（CIO）和德国CLL研究组（GCLLSG）的临床试验中使用患者标本进行治疗和随访，将为我们提供独特的机会，研究CLL患者在整个病程中的临床和分子数据。

Studies in in-depth characterized primary patient material are needed to discover key driver molecules with significant biological and clinical relevance in CLL. Accordingly, it is indispensable to prove new discoveries being dependent or independent of molecular prognostic parameters which have been established previously in CLL. In order to provide all scientists of the CRU-286 with well-defined samples of primary human and murine CLL cells, central diagnostics, genomic analyses and biobanking will be performed within this core project 2 (CP2). Advanced platforms for immunophenotyping, virtual microscopy, image analysis and storing, and advanced translational genomics have been established as collaborative structures at the Institute of Pathology (R. Büttner), the Cologne Center for Genomics (P. Nürnberg) and the Department I of Internal Medicine (Hematology/Oncology, K.-A. Kreuzer, C. Schweighofer). Peripheral blood, bone marrow and tissue specimens including lymph nodes will be morphologically diagnosed and undergo a systematic diagnostic work-up including immunophenotyping, somatic mutation analyses (i.e., TP53, IGHV), fluorescence-in-situ hybridization, and conventional cytogenetics. Further, appropriate protein and nucleic acid extracts will be stored centrally under appropriate data protection and safety requirements. Using a fully operational genomics unit, on-demand whole-genome-, exome, or target enriched gene extracts will undergo deep sequencing with parallel transcriptome and single nucleotide variant (SNV) analyses. The use of patient specimen treated and followed at the University Hospital Cologne (UHC)/Center of Integrated Oncology (CIO) and within clinical trials of the German CLL Study Group (GCLLSG), will provide us with the unique opportunity to study combined clinical and molecular data from CLL patients metachronically over their entire disease course.