Project 466973

Hypertranscription is defined by a global increase of RNA output in a cell. It is an abnormality of a cell's transcriptional machinery best characterized in cancer cell lines and stem cell models. The Shlien lab developed a computational method to measure hypertranscription in thousands of cancers across different adult cancer types, which revealed hypertranscriptions association with aggressive cancer subtypes, and its prognostic utility across adult cancers. Analysis of transcriptomes of individual cells (single cell sequencing) from lung tumors identified groups of hypertranscriptive cells which dominated tumor transcriptional output even when present as a minority cell population. The Shlien labs recent discoveries have elucidated the importance of hypertranscription across adult cancer types, however hypertranscriptions prevalence in pediatric cancers is unknown.The interests of this project lie in understanding the landscape of hypertranscription in pediatric tumours and how cancer cells exhibiting hypertranscription proliferate during tumor growth. To understand hypertranscription in pediatric cancers, genomic data from RNA and DNA sequencing as a part of the SickKids Cancer Sequencing Program (KiCS) will be used. Hypertranscription levels will be measured and compared between cancer types. In single cell sequencing data, hypertranscriptive clones will be identified and tracked over time. Understanding the role of hypertranscriptive clones during tumor evolution will provide fundamental insights into evolution in both adult and pediatric cancers. Results of this project will also nominate candidate tumor types for transcriptional inhibitor therapy and aid in the early identification of aggressive neoplasms.