My Linh Thibodeau
Resolution of germline hereditary cancer structural variants using nanopore sequencing
About My Linh Thibodeau
Dr. My Linh Thibodeau is currently training in the Medical Genetics Residency Program at the University of British Columbia. In 2017, she won entry to the Royal College of Physicians and Surgeons Canada Clinician Investigator Program to apply bioinformatic approaches to the discovery and characterization of hereditary cancer predispositions. During her work in the Personalized OncoGenomics study at BC Cancer in Vancouver, Canada, Dr. Thibodeau acquired expertise in the analysis and integration of whole genome and whole transcriptome datasets. Taken together with her medical training, these experiences have allowed Dr. Thibodeau to develop a unique clinical-bioinformatic skillset.
Structural variants (SVs) are difficult to ascertain using short-read sequencing technology. As part of the Personalized OncoGenomics (POG) study, tumour and matched normal blood Illumina whole-genome sequencing was performed in patients with advanced cancers. We used Oxford Nanopore sequencing for validation and breakpoint resolution of four germline SVs in hereditary cancer genes: 1) ATM deletion, 2) NTHL1-TSC2-TRAF7 complex rearrangements, 3) IFT140-TSC2 inversion and 4) UIMC1-NSD1 complex rearrangements. The 12 breakpoints of these 4 SVs were seen in the nanopore data. Long-read sequencing was necessary for the resolution of SVs and corrected the initial interpretation in 3 out of 4 cases. Our results also showed the suspected IFT140-TSC2 large inversion to be a small intronic inverted duplication event that did not disrupt either gene. Our results suggest that short-read technology may not be sufficient for SVs assessment. Long-read sequencing technology may eventually be considered as an option for the detection and validation of clinically relevant germline SVs.
My Linh Thibodeau