This is a report summary by Dr. Matthew Breen of a recent study of canine histiocytic sarcoma (previously called malignant histiocytosis or histio.) If you want to read the actual article you can see it at:
The "Next Steps" at the end of Dr. Breen's note talks about the study that we are raising money for in our current 2011 Willem Wijnberg Cancer Fundraiser.
The really great thing about the histio research going on with Berners is that Dr. Matthew Breen, Dr. Catherine Andre, and Dr. Elaine Ostrander are sharing information with each other in order to hasten the process of making discoveries about histio.
We need your support to be able to help fund this very important research. Here is the website so you can see how to make a donation to our 8th annual cancer fundraiser:
Thank you, Dr. Breen for your role in the fight against histio!!
Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior
Benoit Hedan, Rachael Thomas, Alison Motsinger-Reif, Jerome Abadie, Catherine Andre, John Cullen and Matthew Breen
BMC Cancer 2011, 11:201doi:10.1186/1471-2407-11-201
Published May 26th 2011
In cancers, the organization of the genetic material may become altered, leading to pieces of DNA being represented with either too few or too many copies. The consequences of such changes can disrupt the regular machinery of the cells and have a major effect on the progression of the cancer. Using DNA isolated from histiocytic tumor (histio) samples submitted from Bernese Mountain Dogs (BMDs) and Flat Coated Retrievers (FCRs) as part of CHF-760, Dr. Breens lab looked for such DNA copy number aberrations (CNAs) across the entire dog genome. They compared the distribution of CNAs between US and French BMDs and between BMD and FCR samples.
The study used BMDs originating from the USA as well as from France (provided by Dr. Andre) and showed that the two populations had the same pattern of CNAs. These data suggest that discoveries resulting from studies of histio in US Berners dogs would also apply to European Berners.
Almost all recurrent CNAs identified in this study were shared between BMD and FCR, suggesting that they are associated more with the cancer phenotype than with breed.
A small number of CNAs were unique to each breed, implying that they may contribute to the major differences in tumor location evident in these two breeds: FCRs are more likely to have an initial mass localized to a joint and then disseminate; BMDs are more prone to be diagnosed with multiple organ involvement.
Key regions of genome involved include segments of dog chromosomes 2, 11, 16, 22 and 31
The CNAs exhibited by histio in both BMD and FCR offer a valuable step forward towards elucidation of the pathophysiological and genetic mechanisms associated with histiocytic malignancies. This study has helped to further our understanding of the propagation and cancerization of histiocytic cells, contributing to development of new and effective therapeutic modalities for both species.
Dr. Breens new grant proposal (submitted to AKC-CHF) aims to assess the CNAs identified in histio at much higher resolution, using new microarrays developed in his lab. While the focus will continue to be on Berners, they will include histio in other breeds as well as human patients. This comparative approach will help refine the key regions in the Berner and allow them to better select histio genes to assess in more detail. This next major step is the basis of a pending research grant submitted to AKC-CHF. Drs. Breen and Andre have shared Berner histio samples with Dr. Ostrander who is also using these cases to look closely at specific regions in the genome.
Dr. Matthew Breen
The 8th Willem Wijnberg Cancer Fundraiser 2011
Histio Roll Call
To fully understand just how important it is that we do all we can to help and fund this research, view the Histio Roll Call Site and see just some of the many beloved Bernese lost to this awful disease.