Genetic switches identified in glioblastoma tumours
Researchers at the US-based Baker Institute for Animal Health, including Mr Tinyi Chu (Croucher Scholarship 2013), have devised a tool to provide further insight into glioblastoma tumours and the genetic “switches” that power the tumours’ growth. Glioblastoma is a devastating cancer found in the brain or spinal cord. Following diagnosis, most patients survive just 15 months, even with treatment.
In a paper in Nature Genetics, lead author Chu and fellow scientists in the lab of assistant professor Charles Danko identified switches in different types of glioblastoma tumours, including those linked to how long a patient survives. The team at the Baker Institute, part of the College of Veterinary Medicine at Cornell University, worked together with State University of New York Upstate Medical University to analyse 20 glioblastoma samples from its tissue bank.
Genes make up just two percent of our genome. Yet cancer and many other diseases are a result of how genes are used. Switches called transcription factors bind to the genome to turn genes on and off, which can trigger the cellular changes that cause disease. To carry out their analysis, the researchers applied and developed a technique called chromatin run-on sequencing (ChRO-seq) that creates a map of active switches and the genes they turn on. “We demonstrated the power of ChRO-seq in detecting transcriptional regulation in almost any kinds of solid tissue, including tissues with heavily degraded RNA,” Chu said.
Leveraging the data resulting from the new technique, the team classified the glioblastomas into subtypes based on which switches were active in the different tumours compared to healthy brain tissues. “We also discovered a core group of transcription factors (switches) that control the expression of genes associated with clinical outcomes,” Chu noted.
Further studies are due to be carried out to determine these switches’ ability to predict which patients will survive longer with glioblastoma. Two of the switches’ connections were previously unknown. In addition, ChRO-seq can be useful for greater understanding of other diseases caused by gene regulation malfunctions, including some heart and autoimmune conditions.
Meanwhile, Chu is hoping to inform personalised treatment plans or assist in the development of new therapies through an analysis of a larger group of glioblastomas that can link active switches in individual tumours with patient survival and treatment outcomes.
Mr Tinyi Chu received the Croucher Scholarship in 2013. He gained his BSc in Biochemistry at the Chinese University of Hong Kong in 2013 (First Honour). During his undergraduate research, he worked on structural biology, biochemistry and microbiology, during which he independently solved the crystal structure of ribosomal maturation factor and studied its related pathogenesis mechanisms. He was a SURF fellow at Caltech in the summer of 2011 and a CSSS Croucher Visiting Scholar of the University of Cambridge in the summer of 2012. After graduation Tinyi started his graduate study at the Cornell University, and switched to the field of statistical learning and computational biology.
To view Mr Chu’s Croucher profile, please click here.