EGAS00001003542-sc-2020-10-05T07:42:12Z - samples

The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. Different patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. Through an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.EGA dataset EGAD00001006427

Mutographs项目旨在通过突变特征（mutational signatures）研究，加深我们对癌症致病机制的理解。该大规模国际研究项目由Mike Stratton牵头，联合Paul Brennan、Ludmil Alexandrov、Allan Balmain、David Phillips与Peter Campbell共同开展，荣获英国癌症研究基金会（Cancer Research UK）重大挑战项目资助。诱发癌症的不同环境、生活方式与遗传因素，会产生各异的体细胞突变（somatic mutation）模式，其中多数机制至今仍未明确。在Mutographs项目框架内，国际癌症研究机构（International Agency for Research on Cancer）正协调在全球5大洲招募5000名癌症患者，涉及结直肠癌、肾癌、胰腺癌、食管腺癌及食管鳞状细胞癌，以探究不同突变特征能否解释癌症发病率的显著差异。简言之，项目依托全球合作伙伴构成的国际网络，采集生物样本，同时收集人口统计学、组织病理学、临床及问卷调研数据。威康桑格研究所（Wellcome Trust Sanger Institute）将对肿瘤-生殖系DNA配对样本进行全基因组测序。随后通过非负矩阵分解（non-negative matrix factorisation）方法提取体细胞突变特征，并与风险因素数据进行关联分析。通过深化对癌症病因学（cancer aetiology）的理解，Mutographs项目的空前研究预计将明确可干预的风险因素，催生全新的癌症预防策略，同时为癌症早筛、精准划分高危人群及推动后续治疗研发提供机遇。EGA数据集EGAD00001006427