Title:

Enabling investigation of gene-environment interactions and cancer risk in pet dogs and cats

Abstract:

Spontaneous cancers in pet dogs and cats are potentially powerful models for investigating gene-environment interactions modulating cancer risk. These companion species share environments with humans and develop cancers that are genomically and clinically similar. Moreover, their shorter lifespans and accelerated disease course facilitate rapid studies. To enable these comparative gene-environment interaction studies in companion animals, we are investigating three main areas. (1) Linking inherited variation to cancer risk: We will perform whole-genome sequencing of samples collected in our direct-to-owner studies, as well as leveraging existing germline sequencing data from 674 dogs. (2) Leveraging passive environmental sampling to measure exposure: For a pilot set of 101 pet dogs, we have deployed a silicone dog tag which absorbs volatile compounds, which can then be identified using mass spectrometry. Preliminary analysis has identified multiple compounds with differential exposure levels between cancer and healthy groups. (3) Characterizing somatic mutations in normal and tumor tissues: We have identified clonal hematopoiesis of indeterminate potential in approximately 10% of dog blood samples. In parallel, we are comparing circulating cell-free DNA between healthy dogs and cats and those with cancer. Together, our work in these areas is advancing comparative studies in companion animals as a powerful framework to accelerate discovery of genetic and environmental factors and interactions leading to somatic mutations and cancer.

Bio:

Dr. Megquier (pronounced McKEAR) is a DVM/PhD postdoctoral researcher in the Karlsson Lab at the Broad Institute, co-mentored by Drs. Elinor Karlsson and Cheryl London. Her work focuses on uncovering the genetic mechanisms of cancer in companion animals. She is currently focused on developing and optimizing the use of blood biopsy in dogs with spontaneously-occurring cancers to inform the use of this powerful technique for patient monitoring and diagnosis in both veterinary and human oncology.