Replication-stress-associated DSBs induced by ionizing radiation risk genomic destabilization and associated clonal evolution

Matsuno, Yusuke; Hyodo, Mai; Suzuki, Mafuka; Tanaka, Yosuke; Horikoshi, Yasunori; Murakami, Yasufumi; Torigoe, Hidetaka; Mano, Hiroyuki; Tashiro, Satoshi; Yoshioka, Ken

doi:10.1016/j.isci.2021.102313

Cited by 14 publications

(29 citation statements)

References 37 publications

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“…A previous in vitro study revealed a correlation between induction of SVs and SNVs within the 1-10 Mb range 17 . To examine SNV induction rates near SV sites in cancer cells directly, the number of SNVs within 1 Mb of an SV site was counted and compared with the random number expected (Fig.…”

Section: Sv-associated Mutagenesis (Snv Induction)mentioning

confidence: 91%

“…The ICGC PCAWG study was searched for validated data on SVs, SNVs, insertion/deletions (indels), mutational signatures, and clinical data (sex, age at diagnosis, and survival time) in patients with breast (BRCA-EU, BRCA-UK), ovarian (OV-AU), pancreatic (PACA-AU, PACA-CA), gastric (GACA-CN), liver (LICA-FR, LINC-JP, LIRI-JP) and prostate (PRAD-CA, PRAD-UK) cancers, and in patients with pancreatic endocrine neoplasms (PAEN-IT, PAEN-AU) and chronic lymphocytic leukemia (CLLE-ES) 18 . Validated data on SVs and SNVs in mouse embryonic fibroblast cells (MEFs) were obtained from a previous study 17 .…”

Section: Methodsmentioning

confidence: 99%

“…This suggests that a type of SNV is induced in association with SVs because deamination-associated SBSs are usually induced in association with Kataegis, i.e., localized hypermutations within 1 kb of SV sites 11,12 . In addition, DNA-repair deficiencies and exogenous DNA damage are widely associated with genomic instability, which often induces SVs [13][14][15] .Recent in vitro studies revealed that clonal evolution of cells with loss of ARF/p53 pathway function can be induced by genomic instability triggered by replication stress-associated DNA double-strand breaks (DSBs) 16,17 . The resulting cells show massive induction of SVs and SNVs; indeed, hotspots of SVs coincide with hotspots of SNVs 17 .…”

mentioning

confidence: 99%

“…Recent in vitro studies revealed that clonal evolution of cells with loss of ARF/p53 pathway function can be induced by genomic instability triggered by replication stress-associated DNA double-strand breaks (DSBs) 16,17 . The resulting cells show massive induction of SVs and SNVs; indeed, hotspots of SVs coincide with hotspots of SNVs 17 .…”

mentioning

confidence: 99%

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Echoed induction of nucleotide variants and chromosomal structural variants in cancer cells

Matsuno¹,

Kusumoto-Matsuo²,

Manaka³

et al. 2022

Sci Rep

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Generally, the number of single-nucleotide variants (SNVs) in somatic cells increases with age, which is expected for replication errors. The number of SNVs in cancer cells, however, is often much higher than that in somatic cells, raising the question of whether cancer cells possess SNV induction pathways. The present study shows that the number of SNVs in cancer cells correlates with the number of chromosomal structural variants (SVs). While Kataegis, localized hypermutations typically arising near SV sites, revealed multiple SNVs within 1 kb, SV-associated SNVs were generally observed within 0.1–1 Mb of SV sites, irrespective of Kataegis status. SNVs enriched within 1 Mb of SV regions were associated with deficiency of DNA damage repair, including HR deficiency-associated single base substitution 3 (SBS3) and exogenous damage-associated SBS7 and SBS36 signatures. We also observed a similar correlation between SVs and SNVs in cells that had undergone clonal evolution in association with genomic instability, implying an association between genomic instability and SV-associated induction of SNVs.

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Section: Sv-associated Mutagenesis (Snv Induction)mentioning

confidence: 91%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Echoed induction of nucleotide variants and chromosomal structural variants in cancer cells

Matsuno¹,

Kusumoto-Matsuo²,

Manaka³

et al. 2022

Sci Rep

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“…The correlation between individual radiosensitivity and SNPs in the BER genes ( LIG1 and NEIL1 ) or DNA repair genes in the NHEJ pathway ( XRCC5 , XRCC6 and XRCC7 ) was reported in human peripheral blood cells of a population exposed to chronic low-level radiation [ 134 ]. Notably, a genomic destabilization has been observed in mouse embryonic fibroblasts after the repair of radiation-induced DSBs due to replication stress-induced DSB accumulation caused by oxidative DNA damage [ 135 ]. Under this condition, cells were more prone to develop single nucleotide variants (SNV), including radiation-associated SNVs.…”

Section: Genetic and Epigenetic Changes Associated With Radiation Carcinogenesis Riskmentioning

confidence: 99%

Genomic Changes Driven by Radiation-Induced DNA Damage and Microgravity in Human Cells

Beheshti

McDonald

Hada

et al. 2021

IJMS

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The space environment consists of a complex mixture of different types of ionizing radiation and altered gravity that represents a threat to humans during space missions. In particular, individual radiation sensitivity is strictly related to the risk of space radiation carcinogenesis. Therefore, in view of future missions to the Moon and Mars, there is an urgent need to estimate as accurately as possible the individual risk from space exposure to improve the safety of space exploration. In this review, we survey the combined effects from the two main physical components of the space environment, ionizing radiation and microgravity, to alter the genetics and epigenetics of human cells, considering both real and simulated space conditions. Data collected from studies on human cells are discussed for their potential use to estimate individual radiation carcinogenesis risk from space exposure.

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Replication stress drives chromosomal instability in fibroblasts of childhood cancer survivors with second primary neoplasms

et al. 2023

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Replication-stress-associated DSBs induced by ionizing radiation risk genomic destabilization and associated clonal evolution

Cited by 14 publications

References 37 publications

Echoed induction of nucleotide variants and chromosomal structural variants in cancer cells

Echoed induction of nucleotide variants and chromosomal structural variants in cancer cells

Genomic Changes Driven by Radiation-Induced DNA Damage and Microgravity in Human Cells

Replication stress drives chromosomal instability in fibroblasts of childhood cancer survivors with second primary neoplasms

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