Refining tumor-associated aneuploidy through ‘genomic recoding’ of recurrent DNA copy number aberrations in 150 canine non-Hodgkin lymphomas

Abstract

Identification of the genomic regions most intimately associated with non-Hodgkin lymphoma (NHL) pathogenesis is confounded by the genetic heterogeneity of human populations. We hypothesize that the restricted genetic variation of purebred dogs, combined with the contrasting architecture of the human and canine karyotypes, will increase the penetrance of fundamental NHL-associated chromosomal aberrations in both species. We surveyed non-random aneuploidy in 150 canine NHL cases, revealing limited genomic instability compared to their human counterparts and no evidence for CDKN2A/B deletion in canine B-cell NHL. ‘Genomic recoding’ of canine NHL data into a ‘virtual human’ chromosome format showed remarkably few regions of copy number aberration (CNA) shared between both species, restricted to regions of dog chromosomes 13 and 31, and human chromosomes 8 and 21. Our data suggest that gene discovery in NHL may be enhanced through comparative studies exploiting the less complex association between CNAs and tumor pathogenesis in canine patients.

Keywords:

• Comparative genomic hybridization (CGH)
• canine
• lymphoma
• chromosome
• microarray

Acknowledgements

This study was supported by funds from the National Institutes of Health (R01CA112211, awarded to M.B.) and the American Kennel Club Canine Health Foundation (CHF615, awarded to M.B. and J.M.). We gratefully acknowledge the expertise of Sandra Horton and the NCSU histopathology laboratory in the preparation and diagnostic evaluation of clinical specimens for this study. We acknowledge the assistance of Drs Andrea Angstadt and Dahlia Nielsen with bioinformatics analysis. We thank Drs Masao Seto, Masao Nakagawa, and Ichiro Takeuchi (Aichi Cancer Center Research Institute, Nagoya, Japan) for assistance with retrieval of raw aCGH data from prior studies of human patients with lymphoma.

Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.