TY  - JOUR
AU  - Bhandari, Vinayak
AU  - Li, Constance H
AU  - Bristow, Robert G
AU  - Boutros, Paul C
AU  - PCAWGConsortium
TI  - Divergent mutational processes distinguish hypoxic and normoxic tumours.
JO  - Nature Communications
VL  - 11
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2021-02569
SP  - 737
PY  - 2020
N1  - siehe Correction: DKFZ Autoren affiliiert im PCAWG Consortium:https://inrepo02.dkfz.de/record/212440 /https://doi.org/10.1038/s41467-022-32339-4
AB  - 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.
KW  - Cell Hypoxia: genetics
KW  - Genes, myc
KW  - Genome, Human
KW  - Genomic Structural Variation
KW  - Humans
KW  - Mutation
KW  - Neoplasms: genetics
KW  - Neoplasms: pathology
KW  - PTEN Phosphohydrolase: genetics
KW  - Polymorphism, Single Nucleotide
KW  - Tumor Hypoxia: genetics
KW  - Tumor Microenvironment: genetics
KW  - Tumor Suppressor Protein p53: genetics
KW  - Whole Genome Sequencing
KW  - TP53 protein, human (NLM Chemicals)
KW  - Tumor Suppressor Protein p53 (NLM Chemicals)
KW  - PTEN Phosphohydrolase (NLM Chemicals)
KW  - PTEN protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:32024819
C2  - pmc:PMC7002770
DO  - DOI:10.1038/s41467-019-14052-x
UR  - https://inrepo02.dkfz.de/record/177482
ER  -