PT  - JOURNAL ARTICLE
AU  - Kristina M Kruglyak
AU  - Jason Chibuk
AU  - Lisa McLennan
AU  - Prachi Nakashe
AU  - Gilberto E Hernandez
AU  - Rita Motalli-Pepio
AU  - Donna M Fath
AU  - John A Tynan
AU  - Lauren E Holtvoigt
AU  - Ilya Chorny
AU  - Daniel S Grosu
AU  - Dana WY Tsui
AU  - Andi Flory
TI  - Blood-based liquid biopsy for comprehensive cancer genomic profiling using next-generation sequencing: an emerging paradigm for noninvasive cancer detection and management in dogs
AID  - 10.1101/2021.05.05.442773
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.05.442773
4099  - http://biorxiv.org/content/early/2021/05/06/2021.05.05.442773.short
4100  - http://biorxiv.org/content/early/2021/05/06/2021.05.05.442773.full
AB  - This proof-of-concept study demonstrates that blood-based liquid biopsy using next generation sequencing of cell-free DNA can noninvasively detect multiple classes of genomic alterations in dogs with cancer, including alterations that originate from spatially separated tumor sites.Eleven dogs with a variety of confirmed cancer diagnoses (including localized and disseminated disease) who were scheduled for surgical resection, and 5 presumably cancer-free dogs, were enrolled. Blood was collected from each subject, and multiple spatially separated tumor tissue samples were collected during surgery from 9 of the cancer subjects.All samples were analyzed using an advanced prototype of a novel liquid biopsy test designed to noninvasively interrogate multiple classes of genomic alterations for the detection, characterization, and management of cancer in dogs.In 5 of the 9 cancer patients with matched tumor and plasma samples, pre-surgical liquid biopsy testing identified genomic alterations, including single nucleotide variants and copy number variants, that matched alterations independently detected in corresponding tumor tissue samples. Importantly, the pre-surgical liquid biopsy test detected alterations observed in spatially separated tissue samples from the same subject, demonstrating the potential of blood-based testing for comprehensive genomic profiling of heterogeneous tumors. Among the 3 patients with post-surgical blood samples, genomic alterations remained detectable in one patient with incomplete tumor resection, suggesting utility for noninvasive detection of minimal residual disease following curative-intent treatment.Liquid biopsy allows for noninvasive profiling of cancer-associated genomic alterations with a simple blood draw and has potential to overcome the limitations of tissue-based testing posed by tissue-level genomic heterogeneity.Competing Interest StatementAll authors are employed by or affiliated with PetDx; and receive compensation from PetDx and/or hold vested or unvested equity in PetDx.