Molecular profiling reveals prognostically significant subtypes of canine lymphoma

A. M. Frantz; A. L. Sarver; D. Ito; T. L. Phang; A. Karimpour-Fard; M. C. Scott; V. E O Valli; K. Lindblad-Toh; K. E. Burgess; B. D. Husbands; M. S. Henson; A. Borgatti; W. C. Kisseberth; L. E. Hunter; M. Breen; T. D. O'Brien; Jaime F. Modiano

doi:10.1177/0300985812465325

Molecular profiling reveals prognostically significant subtypes of canine lymphoma

A. M. Frantz, A. L. Sarver, D. Ito, T. L. Phang, A. Karimpour-Fard, M. C. Scott, V. E O Valli, K. Lindblad-Toh, K. E. Burgess, B. D. Husbands, M. S. Henson, A. Borgatti, W. C. Kisseberth, L. E. Hunter, M. Breen, T. D. O'Brien, Jaime F. Modiano

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Abstract

We performed genomewide gene expression analysis of 35 samples representing 6 common histologic subtypes of canine lymphoma and bioinformatics analyses to define their molecular characteristics. Three major groups were defined on the basis of gene expression profiles: (1) low-grade T-cell lymphoma, composed entirely by T-zone lymphoma; (2) high-grade T-cell lymphoma, consisting of lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma not otherwise specified; and (3) B-cell lymphoma, consisting of marginal B-cell lymphoma, diffuse large B-cell lymphoma, and Burkitt lymphoma. Interspecies comparative analyses of gene expression profiles also showed that marginal B-cell lymphoma and diffuse large B-cell lymphoma in dogs and humans might represent a continuum of disease with similar drivers. The classification of these diverse tumors into 3 subgroups was prognostically significant, as the groups were directly correlated with event-free survival. Finally, we developed a benchtop diagnostic test based on expression of 4 genes that can robustly classify canine lymphomas into one of these 3 subgroups, enabling a direct clinical application for our results.

Original language	English (US)
Pages (from-to)	693-703
Number of pages	11
Journal	Veterinary pathology
Volume	50
Issue number	4
DOIs	https://doi.org/10.1177/0300985812465325
State	Published - Aug 2013

Bibliographical note

Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by grants 2254 (JFM and MB), 615 (JFM, MB, and LEH), and 1113 (TDO and JFM) from the AKC Canine Health Foundation; grant D10-CA-501 (JFM, MB, KLT) from the Golden Retriever Foundation and Morris Animal Foundation; grants P30CA046934 (UCCC Core) and P30CA077598 (MCC Core) from the National Institutes of Health, by the Starlight Fund, the Land of PureGold Foundation, the WillPower Fund, and other philanthropic donations to the University of Minnesota Animal Cancer Care and Research Program and by the Companion Animal Health Foundation and a Tufts University internal seed grants (KEB). AMF was supported by the DVM/PhD combined degree program of the College of Veterinary Medicine, University of Minnesota, by a predoctoral fellowship from Morris Animal Foundation (D09CA-405) and by a doctoral dissertation fellowship from the Graduate School, University of Minnesota. DI is the recipient of a Morris Animal Foundation FIRST Award (D12CA-302). KLT is the recipient of a EURYI award from the ESF.

Keywords

Canine
Gene expression profiling
Lymphoma subclassification
Prognostication

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Frantz, A. M., Sarver, A. L., Ito, D., Phang, T. L., Karimpour-Fard, A., Scott, M. C., Valli, V. E. O., Lindblad-Toh, K., Burgess, K. E., Husbands, B. D., Henson, M. S., Borgatti, A., Kisseberth, W. C., Hunter, L. E., Breen, M., O'Brien, T. D., & Modiano, J. F. (2013). Molecular profiling reveals prognostically significant subtypes of canine lymphoma. Veterinary pathology, 50(4), 693-703. https://doi.org/10.1177/0300985812465325

Frantz, AM, Sarver, AL, Ito, D, Phang, TL, Karimpour-Fard, A, Scott, MC, Valli, VEO, Lindblad-Toh, K, Burgess, KE, Husbands, BD, Henson, MS , Borgatti, A, Kisseberth, WC, Hunter, LE, Breen, M, O'Brien, TD & Modiano, JF 2013, 'Molecular profiling reveals prognostically significant subtypes of canine lymphoma', Veterinary pathology, vol. 50, no. 4, pp. 693-703. https://doi.org/10.1177/0300985812465325

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title = "Molecular profiling reveals prognostically significant subtypes of canine lymphoma",

abstract = "We performed genomewide gene expression analysis of 35 samples representing 6 common histologic subtypes of canine lymphoma and bioinformatics analyses to define their molecular characteristics. Three major groups were defined on the basis of gene expression profiles: (1) low-grade T-cell lymphoma, composed entirely by T-zone lymphoma; (2) high-grade T-cell lymphoma, consisting of lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma not otherwise specified; and (3) B-cell lymphoma, consisting of marginal B-cell lymphoma, diffuse large B-cell lymphoma, and Burkitt lymphoma. Interspecies comparative analyses of gene expression profiles also showed that marginal B-cell lymphoma and diffuse large B-cell lymphoma in dogs and humans might represent a continuum of disease with similar drivers. The classification of these diverse tumors into 3 subgroups was prognostically significant, as the groups were directly correlated with event-free survival. Finally, we developed a benchtop diagnostic test based on expression of 4 genes that can robustly classify canine lymphomas into one of these 3 subgroups, enabling a direct clinical application for our results.",

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author = "Frantz, {A. M.} and Sarver, {A. L.} and D. Ito and Phang, {T. L.} and A. Karimpour-Fard and Scott, {M. C.} and Valli, {V. E O} and K. Lindblad-Toh and Burgess, {K. E.} and Husbands, {B. D.} and Henson, {M. S.} and A. Borgatti and Kisseberth, {W. C.} and Hunter, {L. E.} and M. Breen and O'Brien, {T. D.} and Modiano, {Jaime F.}",

note = "Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by grants 2254 (JFM and MB), 615 (JFM, MB, and LEH), and 1113 (TDO and JFM) from the AKC Canine Health Foundation; grant D10-CA-501 (JFM, MB, KLT) from the Golden Retriever Foundation and Morris Animal Foundation; grants P30CA046934 (UCCC Core) and P30CA077598 (MCC Core) from the National Institutes of Health, by the Starlight Fund, the Land of PureGold Foundation, the WillPower Fund, and other philanthropic donations to the University of Minnesota Animal Cancer Care and Research Program and by the Companion Animal Health Foundation and a Tufts University internal seed grants (KEB). AMF was supported by the DVM/PhD combined degree program of the College of Veterinary Medicine, University of Minnesota, by a predoctoral fellowship from Morris Animal Foundation (D09CA-405) and by a doctoral dissertation fellowship from the Graduate School, University of Minnesota. DI is the recipient of a Morris Animal Foundation FIRST Award (D12CA-302). KLT is the recipient of a EURYI award from the ESF.",

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AU - Scott, M. C.

AU - Valli, V. E O

AU - Lindblad-Toh, K.

AU - Burgess, K. E.

AU - Husbands, B. D.

AU - Henson, M. S.

AU - Borgatti, A.

AU - Kisseberth, W. C.

AU - Hunter, L. E.

AU - Breen, M.

AU - O'Brien, T. D.

AU - Modiano, Jaime F.

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N2 - We performed genomewide gene expression analysis of 35 samples representing 6 common histologic subtypes of canine lymphoma and bioinformatics analyses to define their molecular characteristics. Three major groups were defined on the basis of gene expression profiles: (1) low-grade T-cell lymphoma, composed entirely by T-zone lymphoma; (2) high-grade T-cell lymphoma, consisting of lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma not otherwise specified; and (3) B-cell lymphoma, consisting of marginal B-cell lymphoma, diffuse large B-cell lymphoma, and Burkitt lymphoma. Interspecies comparative analyses of gene expression profiles also showed that marginal B-cell lymphoma and diffuse large B-cell lymphoma in dogs and humans might represent a continuum of disease with similar drivers. The classification of these diverse tumors into 3 subgroups was prognostically significant, as the groups were directly correlated with event-free survival. Finally, we developed a benchtop diagnostic test based on expression of 4 genes that can robustly classify canine lymphomas into one of these 3 subgroups, enabling a direct clinical application for our results.

AB - We performed genomewide gene expression analysis of 35 samples representing 6 common histologic subtypes of canine lymphoma and bioinformatics analyses to define their molecular characteristics. Three major groups were defined on the basis of gene expression profiles: (1) low-grade T-cell lymphoma, composed entirely by T-zone lymphoma; (2) high-grade T-cell lymphoma, consisting of lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma not otherwise specified; and (3) B-cell lymphoma, consisting of marginal B-cell lymphoma, diffuse large B-cell lymphoma, and Burkitt lymphoma. Interspecies comparative analyses of gene expression profiles also showed that marginal B-cell lymphoma and diffuse large B-cell lymphoma in dogs and humans might represent a continuum of disease with similar drivers. The classification of these diverse tumors into 3 subgroups was prognostically significant, as the groups were directly correlated with event-free survival. Finally, we developed a benchtop diagnostic test based on expression of 4 genes that can robustly classify canine lymphomas into one of these 3 subgroups, enabling a direct clinical application for our results.

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Molecular profiling reveals prognostically significant subtypes of canine lymphoma

Abstract

Bibliographical note

Keywords

UN SDGs

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