Signatures of copy number alterations in human cancer
Signatures of copy number alterations in human cancer
ABSTRACT The gains and losses of DNA that emerge as a consequence of mitotic errors and chromosomal instability are prevalent in cancer. These copy number alterations contribute to cancer initiaition, progression and therapeutic resistance. Here, we present a conceptual framework for examining the patterns of copy number alterations in human cancer using whole-genome sequencing, whole-exome sequencing, and SNP6 microarray data making it widely applicable to diverse datasets. Deploying this framework to 9,873 cancers representing 33 human cancer types from the TCGA project revealed a set of 19 copy number signatures that explain the copy number patterns of 93% of TCGA samples. 15 copy number signatures were attributed to biological processes of whole-genome doubling, aneuploidy, loss of heterozygosity, homologous recombination deficiency, and chromothripsis. The aetiology of four copy number signatures are unexplained and some cancer types have unique patterns of amplicon signatures associated with extrachromosomal DNA, disease-specific survival, and gains of proto-oncogenes such as MDM2. In contrast to base-scale mutational signatures, no copy number signature associated with known cancer risk factors. The results provide a foundation for exploring patterns of copy number changes in cancer genomes and synthesise the global landscape of copy number alterations in human cancer by revealing a diversity of mutational processes giving rise to copy number changes.
Van Loo Peter、Hames Shadi、Tarabichi Maxime、Lesluyes Tom、Islam S. M. Ashiqul、Abbasi Ammal、Khandekar Azhar、Alexandrov Ludmil B.、Flanagan Adrienne M.、Mertens Fredrik、Steele Christopher D.、Pillay Nischalan、Haase Kerstin
Cancer Genomics Laboratory, The Francis Crick InstituteResearch Department of Pathology, Cancer Institute, University College LondonCancer Genomics Laboratory, The Francis Crick InstituteCancer Genomics Laboratory, The Francis Crick InstituteDepartment of Cellular and Molecular Medicine, UC San Diego||Department of Bioengineering, UC San Diego||Moores Cancer Center, UC San DiegoDepartment of Cellular and Molecular Medicine, UC San Diego||Department of Bioengineering, UC San Diego||Moores Cancer Center, UC San DiegoDepartment of Cellular and Molecular Medicine, UC San Diego||Department of Bioengineering, UC San Diego||Moores Cancer Center, UC San DiegoDepartment of Cellular and Molecular Medicine, UC San Diego||Department of Bioengineering, UC San Diego||Moores Cancer Center, UC San DiegoResearch Department of Pathology, Cancer Institute, University College London||Department of Cellular and Molecular Pathology, Royal National Orthopaedic Hospital NHS TrustDivision of Clinical Genetics, Department of Laboratory Medicine, Lund University||Department of Clinical Genetics and Pathology, Division of Laboratory MedicineResearch Department of Pathology, Cancer Institute, University College LondonResearch Department of Pathology, Cancer Institute, University College London||Department of Cellular and Molecular Pathology, Royal National Orthopaedic Hospital NHS TrustCancer Genomics Laboratory, The Francis Crick Institute
肿瘤学基础医学生物科学研究方法、生物科学研究技术
Van Loo Peter,Hames Shadi,Tarabichi Maxime,Lesluyes Tom,Islam S. M. Ashiqul,Abbasi Ammal,Khandekar Azhar,Alexandrov Ludmil B.,Flanagan Adrienne M.,Mertens Fredrik,Steele Christopher D.,Pillay Nischalan,Haase Kerstin.Signatures of copy number alterations in human cancer[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2021.04.30.441940.点此复制
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