The majority of human cancers are marked by focal amplifications, amongst other types of somatic damage. Focal amplifications, which involve rearrangements that drive tumor growth and evolution in multiple types of cancers, elicit gain of function alterations in oncogenes. These regions are considered vital hotspots for genomic rearrangements and may undergo rapid copy number changes and structural rearrangements.
Extrachromosomal DNA
Recent research within cancer genomics has demonstrated that cancer cell genomes contain extrachromosomal DNA (ecDNA), elements of DNA not found on the chromosome. Through clinical research, ecDNA was discovered to be common in a majority of cancer subtypes, and to play to a significant role in cancer development and tumor evolution. It takes on this role by contributing to the increased expression of oncogenes due to open chromatin and novel interactions with enhancers that activate transcription of these specific genes. The absence of centromeres in ecDNA results in its arbitrary proliferation across the genome during cell division. Since research has suggested that focal amplifications, as described above, are commonly found on ecDNA, an understanding of the biological mechanisms and features underlying ecDNA proves incredibly important in enhancing cancer therapeutics and diagnostics.
Leader: Rishaan