肿瘤缺氧在基因组不稳定性和肿瘤演化中的作用

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SCI 13 February 2025 Tumour hypoxia in driving genomic instability and tumour evolution (Nature Reviews Cancer, IF: 72.5) Alexandru Suvac, Jack Ashton & Robert G. Bristow CORRESPONDENCE TO: Robert.Bristow@manchester.ac.uk Abstract  摘要 Intratumour hypoxia is a feature of all heterogenous solid tumours. Increased levels or subregions of tumour hypoxia are associated with an adverse clinical prognosis, particularly when this co-occurs with genomic instability. Experimental evidence points to the acquisition of DNA and chromosomal alterations in proliferating hypoxic cells secondary to inhibition of DNA repair pathways such as homologous recombination, base excision repair and mismatch repair. Cell adaptation and selection in repair-deficient cells give rise to a model whereby novel single-nucleotide mutations, structural variants and copy number alterations coexist with altered mitotic control to drive chromosomal instability and aneuploidy. Whole-genome sequencing studies support ………………………………