Chromothripsis followed by circular recombination drives oncogene amplification in human cancer
Carolina Rosswog1,2,3, Christoph Bartenhagen1,2, Anne Welte1,2
1Department of Experimental Pediatric Oncology, University Children's Hospital of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
Abstract:
The mechanisms behind the evolution of complex genomic amplifications in cancer have remained largely unclear. Using whole-genome sequencing data of the pediatric tumor neuroblastoma, we here identified a type of amplification, termed 'seismic amplification', that is characterized by multiple rearrangements and discontinuous copy number levels. Overall, seismic amplifications occurred in 9.9% (274 of 2,756) of cases across 38 cancer types, and were associated with massively increased copy numbers and elevated oncogene expression. Reconstruction of the development of seismic amplification showed a stepwise evolution, starting with a chromothripsis event, followed by formation of circular extrachromosomal DNA that subsequently underwent repetitive rounds of circular recombination. The resulting amplicons persisted as extrachromosomal DNA circles or had reintegrated into the genome in overt tumors. Together, our data indicate that the sequential occurrence of chromothripsis and circular recombination drives oncogene amplification and overexpression in a substantial fraction of human malignancies.
Related Concept Videos
Cancers Originate from Somatic Mutations in a Single Cell
Conservative Site-specific Recombination and Phase Variation
The recognition sites for Cre recombinase called LoxP...
Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Gene Conversion
Exon Recombination
Exon shuffling follows “splice frame rules.” Each exon...
Rous Sarcoma Virus (RSV) and Cancer
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...


