Reading between the lines: molecular characterization of five widely used canine lymphoid tumour cell lines

Abstract

Molecular characterization of tumour cell lines is increasingly regarded as a prerequisite for defining their validity as models of in vivo neoplasia. We present the first comprehensive catalogue of genomic and transcriptional characteristics of five widely used canine lymphoid tumour cell lines. High-resolution microarray-based comparative genomic hybridization defined their unique profiles of genomic DNA copy number imbalance. Multicolour fluorescence in situ hybridization identified aberrant gains of MYC, KIT and FLT3 and deletions of PTEN and CDKN2 in individual cell lines, and also revealed examples of extensive structural chromosome reorganization. Gene expression profiling and RT-PCR analyses defined the relationship between genomic imbalance and transcriptional dysregulation in each cell line, clarifying their relevance as models of discrete functional pathways with biological and therapeutic significance. In combination, these data provide an extensive resource of molecular data for directing the appropriate use of these cell lines as tools for studying canine lymphoid neoplasia.

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

“…aCGH data for ten cBCL cases overlapping with this prior study showed incomplete correlation between the DNA copy number status and transcriptional status of MYC (data not shown). This is consistent with findings in canine osteosarcoma [58] and lymphoid tumor cell lines [59], suggesting that multiple, complex mechanisms are involved in transcriptional control of this oncogene, and correlating with observations in human cBCL [60]. Interestingly, however, while MYC copy number increase is associated with BCL in human patients, in the present study there was no significant difference in the incidence of MYC gain when comparing cBCL (38.9% of cases) and cTCL (29.7% of cases) (p < 0.334).…”

Establishment of Five Canine Lymphoma Cell Lines and Tumor Formation in a Xenotransplantation Model

“…Unexpectedly, PTEN was overexpressed in all five cell lines derived in this study. Previous studies demonstrated decreased PTEN expression due to homozygous deletion on CFA26 in 2 out of 5 cell lines [9], and thus the significance of PTEN overexpression in our cell lines remains to be explored.…”

“…Previous studies have shown that the expression levels of various genes associated with tumorigenesis (MYC, KIT, FLT3, and PTEN) are altered in canine lymphoma cell lines owing to genomic amplification or deletion, as elucidated by CGH analysis [4]. The expression of MYC is often upregulated in canine lymphoma cell lines, partly due to a gain in copy numbers of dog chromosome 13 (CFA13) [9]. Consistent with this study, we observed upregulation of MYC in four of five cell lines.…”

In vitro drug sensitivity in canine lymphoma

“…However, chemosensitivity studies carried out on established cell lines do not always reflect the actual patient situation (18). Therefore, apart from cell-linebased studies, primary culture studies predominate as they better reflect the actual type of malignant cells and their sensitivity to drugs.…”