Non-Mendalian inheritance of extrachromosal DNA elements can drive disease evolution in glioblastoma
Genomic heterogeneity of glioblastoma (GBM) is suspected to contribute to the poor response to therapy of this disease. We compared molecular characteristics between primary GBM, neurospheres and orthotopic xenograft models derived from the same parental tumor. Driver alterations were in majority propagated from tumor to model systems. Extrachromosomal amplifications of MET, a proto-oncogene coding for a receptor tyrosine kinase, were detected in three primary GBM, largely discarded in neurospheres cultures, but resurfaced in xenografts. The clonal dynamics inferred by somatic single nucleotide variants (sSNVs) in MET-amplified samples diverged from the pattern delineated by the MET amplification event suggesting that the MET event and sSNVs were inherited in different manners. Our analysis shows that extrachromosomal elements are able to drive tumor progression.
- Type: Other
- Archiver: European Genome-Phenome Archive (EGA)
Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data
Dataset ID | Description | Technology | Samples |
---|---|---|---|
EGAD00001002214 | Illumina HiSeq 2000 | 64 | |
EGAD00001002219 | Illumina HiSeq 2000 | 82 | |
EGAD00001002245 | Illumina HiSeq 2000 | 82 | |
EGAD00001002264 | PacBio RS II | 2 |
Publications | Citations |
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Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma.
Nat Genet 50: 2018 708-717 |
155 |
Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription.
Cancer Cell 39: 2021 694-707.e7 |
101 |
Unscrambling cancer genomes via integrated analysis of structural variation and copy number.
Cell Genom 2: 2022 100112 |
39 |