Rxivist logo

Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma

By Ana C. deCarvalho, Hoon Kim, Laila M. Poisson, Mary E. Winn, Claudius Mueller, David Cherba, Julie Koeman, Sahil Seth, Alexei Protopopov, Michelle Felicella, Siyuan Zheng, Asha Multani, Yongying Jiang, Jianhua Zhang, Do-Hyun Nam, Emanuel F. Petricoin, Lynda Chin, Tom Mikkelsen, Roel G.W. Verhaak

Posted 14 Oct 2016
bioRxiv DOI: 10.1101/081158 (published DOI: 10.1038/s41588-018-0105-0)

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.

Download data

  • Downloaded 1,863 times
  • Download rankings, all-time:
    • Site-wide: 4,388 out of 94,912
    • In cancer biology: 101 out of 3,367
  • Year to date:
    • Site-wide: 15,425 out of 94,912
  • Since beginning of last month:
    • Site-wide: 31,333 out of 94,912

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News