Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma
Ana C. deCarvalho,
Laila M. Poisson,
Mary E. Winn,
Emanuel F. Petricoin,
Roel G.W. Verhaak
Posted 14 Oct 2016
bioRxiv DOI: 10.1101/081158 (published DOI: 10.1038/s41588-018-0105-0)
Posted 14 Oct 2016
To understand how genomic heterogeneity of glioblastoma (GBM) contributes to the poor response to therapy, which is characteristic of this disease, we performed DNA and RNA sequencing on GBM tumor samples and the neurospheres and orthotopic xenograft models derived from them. We used the resulting data set to show that somatic driver alterations including single nucleotide variants, focal DNA alterations, and oncogene amplification in extrachromosomal DNA (ecDNA) elements were in majority propagated from tumor to model systems. In several instances, ecDNAs and chromosomal alterations demonstrated divergent inheritance patterns and clonal selection dynamics during cell culture and xenografting. Longitudinal patient tumor profiling showed that oncogenic ecDNAs are frequently retained after disease recurrence. Our analysis shows that extrachromosomal elements increase the genomic heterogeneity during tumor evolution of glioblastoma, independent of chromosomal DNA alterations.
- Downloaded 1,814 times
- Download rankings, all-time:
- Site-wide: 3,999 out of 84,293
- In cancer biology: 98 out of 2,951
- Year to date:
- Site-wide: 11,256 out of 84,293
- Since beginning of last month:
- Site-wide: 5,966 out of 84,293
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!