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@ARTICLE{Bhandari:177482,
author = {V. Bhandari and C. H. Li and R. G. Bristow and P. C.
Boutros and PCAWGConsortium},
title = {{D}ivergent mutational processes distinguish hypoxic and
normoxic tumours.},
journal = {Nature Communications},
volume = {11},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2021-02569},
pages = {737},
year = {2020},
note = {siehe Correction: DKFZ Autoren affiliiert im PCAWG
Consortium:https://inrepo02.dkfz.de/record/212440
/https://doi.org/10.1038/s41467-022-32339-4},
abstract = {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.},
keywords = {Cell Hypoxia: genetics / Genes, myc / Genome, Human /
Genomic Structural Variation / Humans / Mutation /
Neoplasms: genetics / Neoplasms: pathology / PTEN
Phosphohydrolase: genetics / Polymorphism, Single Nucleotide
/ Tumor Hypoxia: genetics / Tumor Microenvironment: genetics
/ Tumor Suppressor Protein p53: genetics / Whole Genome
Sequencing / TP53 protein, human (NLM Chemicals) / Tumor
Suppressor Protein p53 (NLM Chemicals) / PTEN
Phosphohydrolase (NLM Chemicals) / PTEN protein, human (NLM
Chemicals)},
cin = {B080 / B240 / B370 / B330 / HD01 / B060 / B360 / BE01 /
B062 / B066 / B063 / W190 / B260 / W610 / B087},
ddc = {500},
cid = {I:(DE-He78)B080-20160331 / I:(DE-He78)B240-20160331 /
I:(DE-He78)B370-20160331 / I:(DE-He78)B330-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)B060-20160331 /
I:(DE-He78)B360-20160331 / I:(DE-He78)BE01-20160331 /
I:(DE-He78)B062-20160331 / I:(DE-He78)B066-20160331 /
I:(DE-He78)B063-20160331 / I:(DE-He78)W190-20160331 /
I:(DE-He78)B260-20160331 / I:(DE-He78)W610-20160331 /
I:(DE-He78)B087-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32024819},
pmc = {pmc:PMC7002770},
doi = {10.1038/s41467-019-14052-x},
url = {https://inrepo02.dkfz.de/record/177482},
}