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Chromosome aberrations in canine multicentric lymphomas detected with comparative genomic hybridisation and a panel of single locus probes.

ABSTRACT: Recurrent chromosome aberrations are frequently observed in human neoplastic cells and often correlate with other clinical and histopathological parameters of a given tumour type. The clinical presentation, histology and biology of many canine cancers closely parallels those of human malignancies. Since humans and dogs demonstrate extensive genome homology and share the same environment, it is expected that many canine cancers will also be associated with recurrent chromosome aberrations. To investigate this, we have performed molecular cytogenetic analyses on 25 cases of canine multicentric lymphoma. Comparative genomic hybridisation analysis demonstrated between one and 12 separate regions of chromosomal gain or loss within each case, involving 32 of the 38 canine autosomes. Genomic gains were almost twice as common as losses. Gain of dog chromosome (CFA) 13 was the most common aberration observed (12 of 25 cases), followed by gain of CFA 31 (eight cases) and loss of CFA 14 (five cases). Cytogenetic and histopathological data for each case are presented, and cytogenetic similarities with human non-Hodgkin's lymphoma are discussed. We have also assembled a panel of 41 canine chromosome-specific BAC probes that may be used for accurate and efficient chromosome identification in future studies of this nature.

SUBMITTER: Thomas R

PROVIDER: S-EPMC2394339 | biostudies-other | 2003 Oct

REPOSITORIES: biostudies-other

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Project description:Lymphoma is the most common hematopoietic tumour in dogs and is remarkably similar to the human disease. Tumour biomarker discovery is providing new tools for diagnostics and predicting therapeutic response and clinical outcome. MicroRNAs are small non-coding RNAs that participate in post-transcriptional gene regulation and their aberrant expression can impact genes involved in cancer. The aim of this study was to characterize microRNA expression in lymph nodes and plasma from dogs with multicentric B or T cell lymphoma compared to healthy control dogs. We further compared expression between lymph nodes and corresponding plasma samples and assessed changes in expression at relapse compared to time of diagnosis. Lastly, we investigated microRNAs for association with clinical outcome in patients treated with CHOP chemotherapy. A customized PCR array was utilized to profile 38 canine target microRNAs. Quantification was performed using real time RT-qPCR and relative expression was determined by the delta-delta Ct method. In lymph nodes, there were 16 microRNAs with significantly altered expression for B cell lymphoma and 9 for T cell lymphoma. In plasma, there were 15 microRNAs altered for B cell lymphoma and 3 for T cell lymphoma. The majority of microRNAs did not have correlated expression between lymph node and plasma and only 8 microRNAs were significantly different between diagnosis and relapse. For B cell lymphoma, 8 microRNAs had differential expression in the non-remission group compared to dogs that completed CHOP in complete remission. Four of these microRNAs were also altered in patients that died prior to one-year. Kaplan-Meier survival curves for high versus low microRNA expression revealed that 10 microRNAs were correlated with progression-free survival and 3 with overall survival. This study highlights microRNAs of interest for canine multicentric lymphoma. Future goals include development of microRNA panels that may be useful as biomarkers with the intent to provide improved outcome prediction to veterinary cancer patients.

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Chromosome aberrations in canine multicentric lymphomas detected with comparative genomic hybridisation and a panel of single locus probes.

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