Microsatellite instability in radiation-induced murine tumours; influence of tumour type and radiation quality

Haines, Jackie; Bacher, Jeffery W.; Coster, Margaret; Huiskamp, R.; Meijne, Emmy; Mancuso, Mariateresa; Pazzaglia, Simonetta; Bouffler, Simon

doi:10.3109/09553001003734600

Cited by 13 publications

(8 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Microsatellites are repeated mono-nucleotide and di-nucleotide sequences that are prone to error during DNA replication. Loss of DNA mismatch repair results in variation of the length of microsatellite sequences in some human tumors, including GBM (21, 22). Both ATRX mutation (1) and microsatellite instability (MSI) (21) are seen more frequently in younger patients with GBM.…”

Section: Resultsmentioning

confidence: 99%

ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma

et al. 2016

View full text Add to dashboard Cite

Recent work in human glioblastoma (GBM) has documented recurrent mutations in the histone chaperone protein ATRX. We developed an animal model of ATRX-deficient GBM and show that loss of ATRX reduces median survival and increases genetic instability. Further, analysis of genome-wide data for human gliomas showed that ATRX mutation is associated with increased mutation rate at the single nucleotide variant (SNV) level. In mouse tumors, ATRX deficiency impairs non-homologous end joining (NHEJ) and increases sensitivity to DNA-damaging agents that induce double-stranded DNA breaks. We propose that ATRX loss results in a genetically unstable tumor, which is more aggressive when left untreated, but is more responsive to double-stranded DNA-damaging agents, resulting in improved overall survival.

show abstract

Section: Resultsmentioning

confidence: 99%

ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Hains et al . found a higher level of MSI in mice irradiated by neutrons . In our results, radiation risk for proximal colon cancer tended to be higher than distal colon cancer, although the difference was not significant.…”

Section: Discussionmentioning

confidence: 99%

Radiation risk of incident colorectal cancer by anatomical site among atomic bomb survivors: 1958–2009

Sugiyama

Misumi

Brenner

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

Radiation effects on colorectal cancer rates, adjusted for smoking, alcohol intake and frequency of meat consumption and body mass index (BMI) by anatomical subsite (proximal colon, distal colon and rectum) were examined in a cohort of 105,444 atomic bomb survivors. Poisson regression methods were used to describe radiation‐associated excess relative risks (ERR) and excess absolute rates (EAR) for the 1958–2009 period. There were 2,960 first primary colorectal cancers including 894 proximal, 871 distal and 1,046 rectal cancers. Smoking, alcohol intake and BMI were associated with subsite‐specific cancer background rates. Significant linear dose–responses were found for total colon (sex‐averaged ERR/Gy for 70 years old exposed at age 30 = 0.63, 95% confidence interval [CI]: 0.34; 0.98), proximal [ERR = 0.80, 95% CI: 0.32; 1.44] and distal colon cancers [ERR = 0.50, 95% CI: 0.04; 0.97], but not for rectal cancer [ERR = 0.023, 95% CI: −0.081; 0.13]. The ERRs for proximal and distal colon cancers were not significantly different (p = 0.41). The ERR decreased with attained age for total colon, but not for proximal colon cancer, and with calendar year for distal colon cancer. The ERRs and EARs did not vary by age at exposure, except for decreasing trend in EAR for proximal colon cancer. In conclusion, ionizing radiation is associated with increased risk of proximal and distal colon cancers. The ERR for proximal cancer persists over time, but that for distal colon cancer decreases. There continues to be no indication of radiation effects on rectal cancer incidence in this population.

show abstract

“…There is considerable, if not complete, overlap between RIGI and the GI observed in some (non-radiation-induced) cancers; for example, in the gross chromosomal changes, so called chromosomal instability, observed in colon cancer [48] (see below and section 2.2.). A distinct type of GI, so-called microsatellite instability [49], also observed in colon cancer [48] (see section 2.2 below), is not thought to be associated with radiation-induced cancer in humans [50, 51] although it has been linked with radiation-induced cancers in vivo [52] and in vitro [53]. However, the radiation-induced gaps [54, 55] or breaks [29, 34] that are considered by some as a type of RIGI are unlikely to figure in (non-radiation-induced) GI, since gaps do not correspond to any known phenotype and breaks are generally lethal events for a cell.…”

Section: Types Of Non-targeted Effectmentioning

confidence: 99%

Non-targeted effects of ionising radiation—Implications for low dose risk

Kadhim¹,

Salomaa²,

Wright³

et al. 2013

Mutation Research/Reviews in Mutation Research

210

149

View full text Add to dashboard Cite

Non-DNA targeted effects of ionizing radiation, which include genomic instability, and a variety of bystander effects including abscopal effects and bystander mediated adaptive response, have raised concerns about the magnitude of low-dose radiation risk. Genomic instability, bystander effects and adaptive responses are powered by fundamental, but not clearly understood systems that maintain tissue homeostasis. Despite excellent research in this field by various groups, there are still gaps in our understanding of the likely mechanisms associated with non-DNA targeted effects, particularly with respect to systemic (human health) consequences at low and intermediate doses of ionizing radiation. Other outstanding questions include links between the different non-targeted responses and the variations in response observed between individuals and cell lines, possibly a function of genetic background. Furthermore, it is still not known what the initial target and early interactions in cells are that give rise to non-targeted responses in neighbouring or descendant cells. This paper provides a commentary on the current state of the field as a result of the Non-targeted effects of ionizing radiation (NOTE) Integrated Project funded by the European Union. Here we critically examine the evidence for non-targeted effects, discuss apparently contradictory results and consider implications for low-dose radiation health effects.

show abstract

Microsatellite instability in radiation-induced murine tumours; influence of tumour type and radiation quality

Cited by 13 publications

References 40 publications

ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma

ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma

Radiation risk of incident colorectal cancer by anatomical site among atomic bomb survivors: 1958–2009

Non-targeted effects of ionising radiation—Implications for low dose risk

Contact Info

Product

Resources

About