ctDNA monitoring using patient-specific sequencing and integration of variant reads
Jonathan C. M. Wan, Katrin Heider, Davina Gale, Suzanne Murphy, Eyal Fisher, Florent Moulière, Andrea Ruiz-Valdepeñas, Ángela Santonja, James Morris, Dineika Chandrananda, Andrea Marshall, Andrew B. Gill, Pui Ying Chan, Emily Barker, Gemma Young, Wendy N. Cooper, Irena Hudecova, Francesco Marass, Richard Mair, Kevin M. Brindle, Grant D. Stewart, Jean Abraham, Carlos Caldas, Doris M. Rassl, Robert C. Rintoul, Constantine Alifrangis, Mark R. Middleton, Ferdia A. Gallagher, Christine Parkinson, Amer Durrani, Ultan McDermott, Christopher G. Smith, Charles Massie, Pippa Corrie, Nitzan Rosenfeld
Abstract
informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to parts per million. This resulted in median area under the curve (AUC) values of 0.98 in advanced cancers and 0.80 in early-stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that INVAR may be applied without requiring personalized sequencing panels so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.