Whole genome sequencing analysis of high confidence variants of B-cell lymphoma in Canis familiaris.

Lymphoma (lymphosarcoma) is the second most frequent cancer in dogs and is clinically comparable to human non-Hodgkin lymphoma. Factors affecting canine lymphoma progression are unknown and complex, but there is evidence that genetic mutations play an important role. We employed Next Gen DNA sequenc...

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Main Authors: Alana Sparks, J Paul Woods, Dorothee Bienzle, Geoffrey A Wood, Brenda Lynn Coomber
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0238183
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author Alana Sparks
J Paul Woods
Dorothee Bienzle
Geoffrey A Wood
Brenda Lynn Coomber
author_facet Alana Sparks
J Paul Woods
Dorothee Bienzle
Geoffrey A Wood
Brenda Lynn Coomber
author_sort Alana Sparks
collection DOAJ
description Lymphoma (lymphosarcoma) is the second most frequent cancer in dogs and is clinically comparable to human non-Hodgkin lymphoma. Factors affecting canine lymphoma progression are unknown and complex, but there is evidence that genetic mutations play an important role. We employed Next Gen DNA sequencing of six dogs with multicentric B-cell lymphoma undergoing CHOP chemotherapy to identify genetic variations potentially impacting response. Paired samples from non-neoplastic tissue (blood mononuclear cells) and lymphoma were collected at the time of diagnosis. Cases with progression free survival above the median of 231 days were grouped as 'good' responders and cases below the median were categorized as 'poor' responders. The average number of variants found was 17,138 per case. The variants were filtered to examine those with predicted moderate or high impacts. Many of the genes with variants had human orthologs with links to cancer, but the majority of variants were not previously reported in canine or human lymphoma. Seven genes had variants found in the cancers of at least two 'poor' responders but in no 'good' responders: ATRNL1, BAIAP2L2, ZNF384, ST6GALNAC5, ENSCAFG00000030179 (human ortholog: riboflavin kinase RFK), ENSCAFG00000029320, and ENSCAFG00000007370 (human ortholog: immunoglobin IGKV4-1). Two genes had variants found in the cancers of at least two 'good' responders but in no 'poor' responders: COX18 and ENSCAFG00000030512. ENSCAFG00000030512 has no reported orthologue in any other species. The role of these mutations in the progression of canine lymphoma requires further functional analyses and larger scale study.
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spelling doaj.art-65fa26e341204f09ba73e4d41944ae9c2022-12-21T19:18:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01158e023818310.1371/journal.pone.0238183Whole genome sequencing analysis of high confidence variants of B-cell lymphoma in Canis familiaris.Alana SparksJ Paul WoodsDorothee BienzleGeoffrey A WoodBrenda Lynn CoomberLymphoma (lymphosarcoma) is the second most frequent cancer in dogs and is clinically comparable to human non-Hodgkin lymphoma. Factors affecting canine lymphoma progression are unknown and complex, but there is evidence that genetic mutations play an important role. We employed Next Gen DNA sequencing of six dogs with multicentric B-cell lymphoma undergoing CHOP chemotherapy to identify genetic variations potentially impacting response. Paired samples from non-neoplastic tissue (blood mononuclear cells) and lymphoma were collected at the time of diagnosis. Cases with progression free survival above the median of 231 days were grouped as 'good' responders and cases below the median were categorized as 'poor' responders. The average number of variants found was 17,138 per case. The variants were filtered to examine those with predicted moderate or high impacts. Many of the genes with variants had human orthologs with links to cancer, but the majority of variants were not previously reported in canine or human lymphoma. Seven genes had variants found in the cancers of at least two 'poor' responders but in no 'good' responders: ATRNL1, BAIAP2L2, ZNF384, ST6GALNAC5, ENSCAFG00000030179 (human ortholog: riboflavin kinase RFK), ENSCAFG00000029320, and ENSCAFG00000007370 (human ortholog: immunoglobin IGKV4-1). Two genes had variants found in the cancers of at least two 'good' responders but in no 'poor' responders: COX18 and ENSCAFG00000030512. ENSCAFG00000030512 has no reported orthologue in any other species. The role of these mutations in the progression of canine lymphoma requires further functional analyses and larger scale study.https://doi.org/10.1371/journal.pone.0238183
spellingShingle Alana Sparks
J Paul Woods
Dorothee Bienzle
Geoffrey A Wood
Brenda Lynn Coomber
Whole genome sequencing analysis of high confidence variants of B-cell lymphoma in Canis familiaris.
PLoS ONE
title Whole genome sequencing analysis of high confidence variants of B-cell lymphoma in Canis familiaris.
title_full Whole genome sequencing analysis of high confidence variants of B-cell lymphoma in Canis familiaris.
title_fullStr Whole genome sequencing analysis of high confidence variants of B-cell lymphoma in Canis familiaris.
title_full_unstemmed Whole genome sequencing analysis of high confidence variants of B-cell lymphoma in Canis familiaris.
title_short Whole genome sequencing analysis of high confidence variants of B-cell lymphoma in Canis familiaris.
title_sort whole genome sequencing analysis of high confidence variants of b cell lymphoma in canis familiaris
url https://doi.org/10.1371/journal.pone.0238183
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