Mutated human oncogene recombinant nucleosomes as reference materials for liquid biopsy

血浆样本循环肿瘤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。这一前景受到ctDNA测序工作流程标准化不佳的阻碍，特别是在分析前阶段。目前可用的控制材料有限，已发表的方法通常采用合成寡核苷酸。然而，ctDNA不作为游离核酸循环，而主要作为核小体（dna -组蛋白复合物）循环。Volition是生产重组核小体的世界领先者。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标准材料的要求，以控制、监测和标准化液体活检端到端过程，从分析前无细胞DNA （cfDNA）提取到技术/分析验证，以及临床样品收集和分析的质量控制。拟议的项目将涉及重组核小体材料在数量、纯度、聚集性、完整性和稳定性方面的特征，以及它们与原生患者核小体的可交换性。

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.