Michael Lee: Next Generation Sequencing Strategies to Investigate Telomeres in Cancer
Final Ph.D. Seminar
Location:Children's Medical Research Institute Seminar Room
Michael Lee, Graduate Student, Telomere Length Regulation Unit, Children’s Medical Research Institute
Host: Hilda Pickett
Telomeres are regions of repetitive DNA at the ends of human chromosomes that function to maintain the integrity of the genome. In order for cancers to gain replicative immortality, they are required to activate a telomere maintenance mechanism (TMM), of which there are two: the enzyme telomerase, or the Alternative Lengthening of Telomeres (ALT) pathway. The molecular pathways involved with the selective activation of one TMM over the other remain unclear. In the last decade, whole genome sequencing (WGS) has proven to be an invaluable tool for the study of cancer, leading to the creation of vast cancer WGS data resources, in particular The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). These provide excellent resources from which we can better understand and associate genetic markers and telomere sequence content across cancers, as well as between tumours that utilise telomerase and ALT. In order to utilise these available datasets, we require a WGS-based approach to determine the TMM status of a tumour, as experimental validation requires obtaining cellular material. In this study, we investigate the utility of next generation sequencing to study telomere sequence content, developing strategies to account for sequencing error in repetitive sequences, and demonstrate how it can be applied to delineate telomerase and ALT using WGS data alone in order to further study the molecular pathways associated with ALT activation across tumour subtypes.