Evolution and genomic signatures of spontaneous somatic mutation in Drosophila intestinal stem cells
| Autor: | Allison J. Bardin, Katarzyna Siudeja, Benjamin Boumard, Marius van den Beek, Nick Riddiford |
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| Přispěvatelé: | Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Bardin, Allison |
| Rok vydání: | 2021 |
| Předmět: |
[SDV]Life Sciences [q-bio]
03 medical and health sciences 0302 clinical medicine Germline mutation Genetic model Genetics medicine Animals Indel Evolutionary dynamics Drosophila Genetics (clinical) 030304 developmental biology 0303 health sciences biology Research Stem Cells Cancer Genomics biology.organism_classification medicine.disease [SDV] Life Sciences [q-bio] Intestines Drosophila melanogaster Cancer evolution Mutation Stem cell 030217 neurology & neurosurgery |
| Zdroj: | Genome Res |
| ISSN: | 1549-5469 1088-9051 |
| Popis: | Spontaneous mutations can alter tissue dynamics and lead to cancer initiation. While large-scale sequencing projects have illustrated processes that influence somatic mutation and subsequent tumour evolution, the mutational dynamics operating in the very early stages of cancer development are currently not well understood. In order to explore mutational dynamics in the early stages of cancer evolution we exploited neoplasia arising spontaneously in the Drosophila intestine. We analysed whole-genome sequencing data through the development of a dedicated bioinformatic pipeline to detect structural variants, single nucleotide variants, and indels. We found neoplasia formation to be driven largely through the inactivation of Notch by structural variants, many of which involve highly complex genomic rearrangements. Strikingly, the genome-wide mutational burden of neoplasia - at six weeks of age - was found to be similar to that of several human cancers. Finally, we identified genomic features associated with spontaneous mutation and defined the evolutionary dynamics and mutational landscape operating within intestinal neoplasia over the short lifespan of the adult fly. Our findings provide unique insight into mutational dynamics operating over a short time scale in the genetic model system, Drosophila melanogaster. |
| Databáze: | OpenAIRE |
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