Amplicon rearrangements during the extrachromosomal and intrachromosomal amplification process in a glioma.

ABSTRACT: The mechanisms of gene amplification in tumour cells are poorly understood and the relationship between extrachromosomal DNA molecules, named double minutes (dmins), and intrachromosomal homogeneously staining regions (hsr) is not documented at nucleotide resolution. Using fluorescent in situ hybridization and whole genome sequencing, we studied a xenografted human oligodendroglioma where the co-amplification of the EGFR and MYC loci was present in the form of dmins at early passages and of an hsr at later passages. The amplified regions underwent multiple rearrangements and deletions during the formation of the dmins and their transformation into hsr. In both forms of amplification, non-homologous end-joining and microhomology-mediated end-joining rather than replication repair mechanisms

SUBMITTER: Vogt N 

PROVIDER: S-EPMC4245956 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature