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Blood-based liquid biopsy for comprehensive cancer genomic profiling using next-generation sequencing: an emerging paradigm for noninvasive cancer detection and management in dogs

Kristina M Kruglyak, View ORCID ProfileJason Chibuk, Lisa McLennan, Prachi Nakashe, Gilberto E Hernandez, Rita Motalli-Pepio, Donna M Fath, John A Tynan, Lauren E Holtvoigt, Ilya Chorny, Daniel S Grosu, Dana WY Tsui, Andi Flory
doi: https://doi.org/10.1101/2021.05.05.442773
Kristina M Kruglyak
1PetDx
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Jason Chibuk
1PetDx
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  • ORCID record for Jason Chibuk
Lisa McLennan
1PetDx
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Prachi Nakashe
1PetDx
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Gilberto E Hernandez
1PetDx
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Rita Motalli-Pepio
1PetDx
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Donna M Fath
1PetDx
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John A Tynan
1PetDx
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Lauren E Holtvoigt
1PetDx
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Ilya Chorny
1PetDx
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Daniel S Grosu
1PetDx
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Dana WY Tsui
1PetDx
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  • For correspondence: dtsui@petdx.com
Andi Flory
1PetDx
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Abstract

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 Statement

All authors are employed by or affiliated with PetDx; and receive compensation from PetDx and/or hold vested or unvested equity in PetDx.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 06, 2021.
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Blood-based liquid biopsy for comprehensive cancer genomic profiling using next-generation sequencing: an emerging paradigm for noninvasive cancer detection and management in dogs
Kristina M Kruglyak, Jason Chibuk, Lisa McLennan, Prachi Nakashe, Gilberto E Hernandez, Rita Motalli-Pepio, Donna M Fath, John A Tynan, Lauren E Holtvoigt, Ilya Chorny, Daniel S Grosu, Dana WY Tsui, Andi Flory
bioRxiv 2021.05.05.442773; doi: https://doi.org/10.1101/2021.05.05.442773
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Blood-based liquid biopsy for comprehensive cancer genomic profiling using next-generation sequencing: an emerging paradigm for noninvasive cancer detection and management in dogs
Kristina M Kruglyak, Jason Chibuk, Lisa McLennan, Prachi Nakashe, Gilberto E Hernandez, Rita Motalli-Pepio, Donna M Fath, John A Tynan, Lauren E Holtvoigt, Ilya Chorny, Daniel S Grosu, Dana WY Tsui, Andi Flory
bioRxiv 2021.05.05.442773; doi: https://doi.org/10.1101/2021.05.05.442773

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