Pan-cancer analysis of whole genomes

Nature, Journal Year: 2020, Volume and Issue: 578(7793), P. 82 - 93

Published: Feb. 5, 2020

Abstract Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation this variation at whole-genome scale 1–3 . Here we report integrative analysis 2,658 whole-cancer genomes their matching normal tissues across 38 tumour types from Pan-Cancer Analysis Whole Genomes (PCAWG) Consortium International Genome (ICGC) The Atlas (TCGA). We describe generation PCAWG resource, facilitated international data sharing using compute clouds. On average, cancer contained 4–5 driver mutations when combining coding non-coding genomic elements; however, in around 5% cases no drivers were identified, suggesting that discovery not yet complete. Chromothripsis, which many clustered structural variants arise a single catastrophic event, frequently an early event evolution; acral melanoma, for example, these events precede most somatic point affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate low replicative activity show mechanisms preventing attrition to critical levels. Common rare germline patterns mutation, including mutations, retrotransposition. A collection papers describes drive beyond those TERT promoter 4 ; identifies new signatures mutational processes cause base substitutions, small insertions deletions 5,6 analyses timings evolution 7 diverse transcriptional consequences mutation on splicing, expression levels, fusion 8,9 evaluates range more-specialized features 8,10–18

Language: Английский

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Oxidative Stress in Cancer

Cancer Cell, Journal Year: 2020, Volume and Issue: 38(2), P. 167 - 197

Published: July 9, 2020

Language: Английский

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A compendium of mutational cancer driver genes

Nature reviews. Cancer, Journal Year: 2020, Volume and Issue: 20(10), P. 555 - 572

Published: Aug. 10, 2020

Language: Английский

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Somatic mutant clones colonize the human esophagus with age

Science, Journal Year: 2018, Volume and Issue: 362(6417), P. 911 - 917

Published: Oct. 19, 2018

The mutational burden of aging As people age, they accumulate somatic mutations in healthy cells. About 25% cells normal, sun-exposed skin harbor cancer driver mutations. What about tissues not exposed to powerful mutagens like ultraviolet light? Martincorena et al. performed targeted gene sequencing normal esophageal epithelium from nine human donors varying age (see the Perspective by Chanock). mutation rate was lower esophagus than skin, but there a strong positive selection clones carrying 14 cancer-associated genes. By middle more half colonized mutant clones. Interestingly, NOTCH1 were common cancer. Science , this issue p. 911 ; see also 893

Language: Английский

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Pan-cancer whole-genome analyses of metastatic solid tumours

Nature, Journal Year: 2019, Volume and Issue: 575(7781), P. 210 - 216

Published: Oct. 23, 2019

Abstract Metastatic cancer is a major cause of death and associated with poor treatment efficacy. A better understanding the characteristics late-stage required to help adapt personalized treatments, reduce overtreatment improve outcomes. Here we describe largest, our knowledge, pan-cancer study metastatic solid tumour genomes, including whole-genome sequencing data for 2,520 pairs normal tissue, analysed at median depths 106× 38×, respectively, surveying more than 70 million somatic variants. The characteristic mutations lesions varied widely, that reflect those primary types, high rates duplication events (56%). Individual were relatively homogeneous, vast majority (96%) driver being clonal up 80% tumour-suppressor genes inactivated bi-allelically by different mutational mechanisms. Although genomes showed similar landscape tumours, find could contribute responsiveness therapy or resistance in individual patients. We implement an approach review clinically relevant associations their potential actionability. For 62% patients, identify genetic variants may be used stratify patients towards therapies either have been approved are clinical trials. This demonstrates importance comprehensive genomic profiling precision medicine cancer.

Language: Английский

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The hallmarks of cancer metabolism: Still emerging

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(3), P. 355 - 377

Published: Feb. 4, 2022

Language: Английский

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The landscape of somatic mutation in normal colorectal epithelial cells

Nature, Journal Year: 2019, Volume and Issue: 574(7779), P. 532 - 537

Published: Oct. 23, 2019

Language: Английский

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Intratumoral heterogeneity in cancer progression and response to immunotherapy

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(2), P. 212 - 224

Published: Feb. 1, 2021

Language: Английский

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Context is everything: aneuploidy in cancer

Nature Reviews Genetics, Journal Year: 2019, Volume and Issue: 21(1), P. 44 - 62

Published: Sept. 23, 2019

Language: Английский

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Age-related remodelling of oesophageal epithelia by mutated cancer drivers

Nature, Journal Year: 2018, Volume and Issue: 565(7739), P. 312 - 317

Published: Dec. 24, 2018

Language: Английский

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