Genomics

Dataset Information

0

5- FU treated organoids


ABSTRACT: 5-Fluorouracil (5-FU) is a chemotherapeutic drug component that is commonly used for the treatment of solid cancers. The anticancer properties of 5-FU have been attributed to interference with nucleotide synthesis and through direct incorporation into the DNA as being a pyrimidine analog. As both mechanisms of action may have a mutational impact on surviving tumor cells, we performed three independent analyses to characterize the genomic consequences of 5-FU treatment: i) in vitro treatment of intestinal organoids with 5-FU followed by whole genome sequencing, ii) genome-wide mutation analyses in tumor samples from 5-FU treated patients with breast or colorectal cancer, and iii) analysis of paired biopsies from patients treated with 5-FU between biopsies. Our results demonstrate that both in vitro and in vivo 5-FU causes a mutational pattern that is dominated by T>G substitutions in a CTT context and with strong resemblance to COSMIC signature 17. Interestingly, this signature is also found in non 5-FU treated patients, most prominently in esophageal tumors, indicating that distinct endogenous and exogenous triggers can converge into highly similar mutational signatures. Furthermore, our results suggest that 5-FU may have adverse mutagenic effects on healthy cells and contributes to genetic variability in surviving cancer cells thereby contributing to tumor evolution.

PROVIDER: EGAS00001003592 | EGA |

REPOSITORIES: EGA

Similar Datasets

2012-11-16 | E-GEOD-42318 | biostudies-arrayexpress
2013-03-16 | E-GEOD-45224 | biostudies-arrayexpress
2020-02-26 | GSE145894 | GEO
2018-06-25 | PXD008440 | Pride
2013-03-16 | GSE45224 | GEO
2013-09-01 | E-GEOD-40976 | biostudies-arrayexpress
2014-01-18 | GSE54185 | GEO
2010-05-17 | GSE18378 | GEO
2018-04-09 | GSE103990 | GEO
2012-11-16 | GSE42318 | GEO