Oncogene circularization is a frequent genomic rearrangement in neuroblastoma – Biologisk Institut - Københavns Universitet

BIO > Formidling > Seminarer > Kommende seminarer > Oncogene circularizati...

Oncogene circularization is a frequent genomic rearrangement in neuroblastoma

Speaker: Dr Anton Henssen, Memorial Sloan Kettering Cancer Center, New York, U.S.A.
Host: Birgitte Regenberg, Section for Ecology and Evolution

Extrachromosomal circularization and amplification of oncogenes can efficiently contribute to tumorigenesis. Neuroblastoma, the most common childhood tumor, is a prototypical example for this phenomenon and is characterized by recurrent extrachromosomal circularization and amplification of the MYCN oncogene. The genome-wide frequency and functional consequence of oncogene circularization in neuroblastoma, however, is still unknown. Here we provide a detailed map of the neuroblastoma circulome. We used Circle-seq, a method for circular DNA isolation and sequencing as well as single molecule real time sequencing (SMRT) combined with whole-genome sequencing of neuroblastoma primary tumors and cell lines to detect oncogene circularization genome-wide. We found known driver oncogenes to be recurrently circularized in neuroblastoma, thereby increasing transcript levels. Additionally, we reveal previously uncharacterized recurrent circularization of genes, exons and 3’untranslated regions in neuroblastoma tumors and cell lines. Our results demonstrate that oncogene circularization is a frequent genomic rearrangement in neuroblastoma. We anticipate our findings of oncogene circularization to be a starting point for more in depth analysis of this phenomenon in other cancer entities. Furthermore, our findings suggest that the analysis of tumor circulomes may represent a powerful approach to identify novel oncogenic aberrations in cancer.