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

Kruglyak, K. M.; Chibuk, J.; McLennan, L.; Nakashe, P.; Hernandez, G. E.; Motalli-Pepio, R.; Fath, D. M.; Tynan, J. A.; Holtvoigt, L. E.; Chorny, I.; Grosu, D. S.; Tsui, D. W.; Flory, A.

doi:10.1101/2021.05.05.442773

bioRxiv · 10.1101/2021.05.05.442773

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

Kruglyak, K. M.·Chibuk, J.·McLennan, L.·Nakashe, P.·Hernandez, G. E.·Motalli-Pepio, R.·Fath, D. M.·Tynan, J. A.·Holtvoigt, L. E.·Chorny, I.·Grosu, D. S.·Tsui, D. W.·Flory, A.

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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.

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Kruglyak, K. M., Chibuk, J., McLennan, L., Nakashe, P., Hernandez, G. E., Motalli-Pepio, R., Fath, D. M., Tynan, J. A., Holtvoigt, L. E., Chorny, I., Grosu, D. S., Tsui, D. W., Flory, A.. 2021-05-06. Blood-based liquid biopsy for comprehensive cancer genomic profiling using next-generation sequencing: an emerging paradigm for noninvasive cancer detection and management in dogs. https://doi.org/10.1101/2021.05.05.442773

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