Divergent mutational processes distinguish hypoxic and normoxic tumours

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Bhandari, VinayakUniversity of Toronto (author)

Divergent mutational processes distinguish hypoxic and normoxic tumours

Article/chapterEnglish2020

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2020-02-05
Springer Science and Business Media LLC,2020
10 s.

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LIBRIS-ID:oai:lup.lub.lu.se:79ce5783-20b3-4601-81d1-eb1ad7b83d43
https://lup.lub.lu.se/record/79ce5783-20b3-4601-81d1-eb1ad7b83d43URI
https://doi.org/10.1038/s41467-019-14052-xDOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:143002709URI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

Notes

Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations in TP53, MYC and PTEN are enriched in hypoxic tumours, and mutations in PTEN interact with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
Cell Hypoxia/genetics
Genes, myc
Genome, Human
Genomic Structural Variation
Humans
Mutation
Neoplasms/genetics
PTEN Phosphohydrolase/genetics
Polymorphism, Single Nucleotide
Tumor Hypoxia/genetics
Tumor Microenvironment/genetics
Tumor Suppressor Protein p53/genetics
Whole Genome Sequencing

Added entries (persons, corporate bodies, meetings, titles ...)

Li, Constance HUniversity of Toronto (author)
Bristow, Robert GUniversity of Manchester (author)
Boutros, Paul CUniversity of Toronto (author)
Borg, ÅkeLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Familjär bröstcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Familial Breast Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)onk-abo (creator_code:cre_t)
Ringnér, MarkusLund University,Lunds universitet,Molekylär cellbiologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Molecular Cell Biology,Department of Biology,Faculty of Science(Swepub:lu)thep-mri (creator_code:cre_t)
Staaf, JohanLund University,Lunds universitet,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/lungcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Research Group Lung Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/lungcancer,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-jst (creator_code:cre_t)
University of TorontoUniversity of Manchester (creator_code:org_t)
PCAWG Consortium

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In:Nature Communications: Springer Science and Business Media LLC112041-1723

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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