Mutated human oncogene recombinant nucleosomes as reference materials for liquid biopsy

血浆样本的循环肿瘤DNA（ctDNA）测序在临床肿瘤学实践中变得越来越普遍，并有望彻底改变癌症疾病的诊断和管理。ctDNA测序工作流程标准化不佳阻碍了这一前景，特别是在预分析阶段。有限的控制材料是目前可用的和公开的方法通常应用合成的寡核苷酸。然而，ctDNA并不以游离核酸的形式循环，而是主要以核小体（DNA-组蛋白复合物）的形式循环。Volition是生产重组核小体的世界领导者。这些是单核蛋白复合物，其结构与癌症患者血液中循环的突变ctDNA相同。这些材料有可能满足国际液体活检标准化联盟对参考材料的要求，以控制、监测和验证从分析前游离DNA（cfDNA）提取到技术/测定验证的液体活检端到端过程，以及临床样本采集和分析的QC。拟议项目将涉及重组核小体材料的数量表征，纯度、聚集、完整性和稳定性以及它们相对于天然患者核小体的可重复性。

Circulating tumour DNA (ctDNA) sequencing of plasma samples is becoming commonplace in clinical oncology practice and holds the promise to revolutionise cancer disease diagnosis and management. This promise is impeded by poor standardisation of ctDNA sequencing workflows, particularly in the pre-analytical phase. Limited control materials are currently available and published approaches often apply synthetic oligonucleotides. However, ctDNA does not circulate as free nucleic acid but predominantly as nucleosomes (DNA-histone protein complexes).Volition is the world leader in the production of recombinant-nucleosomes. These are single nucleoprotein complexes designed with the same structure in which mutated ctDNA circulates in the blood of cancer patients. These materials have the potential to fulfil the requirements of the International Liquid Biopsy Standardization Alliance for reference materials to control, monitor and standardise liquid biopsy end-to-end process from pre-analytic cell-free DNA (cfDNA) extraction through technology/assay validation and for QC of clinical sample collection and analysis.The proposed project will involve the characterisation of recombinant-nucleosome materials in terms of quantity, purity, aggregation, integrity and stability as well as their commutability with respect to native patient nucleosomes.