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Pan-cancer whole-genome analyses of metastatic solid tumours

Nature (London), 2019-11, Vol.575 (7781), p.210-216 [Peer Reviewed Journal]

COPYRIGHT 2019 Nature Publishing Group ;COPYRIGHT 2019 Nature Publishing Group ;Copyright Nature Publishing Group Nov 7, 2019 ;The Author(s) 2019 ;ISSN: 0028-0836 ;EISSN: 1476-4687 ;DOI: 10.1038/s41586-019-1689-y ;PMID: 31645765

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Title:
Pan-cancer whole-genome analyses of metastatic solid tumours
Author: Priestley, Peter ; Baber, Jonathan ; Lolkema, Martijn P ; Steeghs, Neeltje ; de Bruijn, Ewart ; Shale, Charles ; Duyvesteyn, Korneel ; Haidari, Susan ; van Hoeck, Arne ; Onstenk, Wendy ; Roepman, Paul ; Voda, Mircea ; Bloemendal, Haiko J ; Tjan-Heijnen, Vivianne C G ; van Herpen, Carla M L ; Labots, Mariette ; Witteveen, Petronella O ; Smit, Egbert F ; Sleijfer, Stefan ; Voest, Emile E ; Cuppen, Edwin
Subjects: Analysis ; Bioinformatics ; Cancer ; Cancer therapies ; Clinical trials ; Clone Cells - metabolism ; Clone Cells - pathology ; Colorectal cancer ; Disease ; DNA Copy Number Variations ; DNA sequencing ; Female ; Gene sequencing ; Genes ; Genetic aspects ; Genetic variance ; Genomes ; Humans ; INDEL Mutation ; Information Dissemination ; Lesions ; Male ; Metastases ; Metastasis ; Mutation ; Neoplasm Metastasis - genetics ; Neoplasms - genetics ; Neoplasms - pathology ; Nucleotide sequencing ; Oncology, Experimental ; Patients ; Precision Medicine ; Prostate ; Signatures ; Solid tumors ; Surveying ; Tissue analysis ; Tumors ; Whole Genome Sequencing
Is Part Of: Nature (London), 2019-11, Vol.575 (7781), p.210-216
Description: Metastatic cancer is a major cause of death and is associated with poor treatment efficacy. A better understanding of the characteristics of late-stage cancer is required to help adapt personalized treatments, reduce overtreatment and improve outcomes. Here we describe the largest, to our knowledge, pan-cancer study of metastatic solid tumour genomes, including whole-genome sequencing data for 2,520 pairs of tumour and normal tissue, analysed at median depths of 106× and 38×, respectively, and surveying more than 70 million somatic variants. The characteristic mutations of metastatic lesions varied widely, with mutations that reflect those of the primary tumour types, and with high rates of whole-genome duplication events (56%). Individual metastatic lesions were relatively homogeneous, with the vast majority (96%) of driver mutations being clonal and up to 80% of tumour-suppressor genes being inactivated bi-allelically by different mutational mechanisms. Although metastatic tumour genomes showed similar mutational landscape and driver genes to primary tumours, we find characteristics that could contribute to responsiveness to therapy or resistance in individual patients. We implement an approach for the review of clinically relevant associations and their potential for actionability. For 62% of patients, we identify genetic variants that may be used to stratify patients towards therapies that either have been approved or are in clinical trials. This demonstrates the importance of comprehensive genomic tumour profiling for precision medicine in cancer.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 0028-0836
EISSN: 1476-4687
DOI: 10.1038/s41586-019-1689-y
PMID: 31645765
Source: ProQuest One Psychology
MEDLINE
ProQuest Central

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Pan-cancer whole-genome analyses of metastatic solid tumours

COPYRIGHT 2019 Nature Publishing Group ;COPYRIGHT 2019 Nature Publishing Group ;Copyright Nature Publishing Group Nov 7, 2019 ;The Author(s) 2019 ;ISSN: 0028-0836 ;EISSN: 1476-4687 ;DOI: 10.1038/s41586-019-1689-y ;PMID: 31645765

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