Epigenetic Biomarkers of B Cell Lymphoma

10/31/2022
Author: Sharon M. Albright, DVM, CCRT

Lymphoma Basics –
Canine lymphoma is a cancer of specific immune system cells known as lymphocytes. The two main types of lymphocytes are B cells and T cells, each with different immune functions. Tumors can occur anywhere that lymphocytes reside or travel in the body – such as the lymph nodes, spleen, or bone marrow. Clinical signs depend on exactly which cells are cancerous and where the cancer starts in the body, among other things. The most common clinical presentation is a dog with enlarged peripheral lymph nodes and varying degrees of malaise (lethargy, decreased appetite). Lymphoma can be easily diagnosed with a biopsy taken with a needle or by removing lymph node tissue and is often very responsive to chemotherapy.

Cancerous canine B cells show a distinct increase in overall methylation compared to normal canine B cells.

Characterizing Canine Lymphoma –
We now recognize that there are many subtypes of canine lymphoma, based on the genetic and molecular features of the cancerous cells. Aggressive B cell lymphoma is common in dogs, especially in the Golden Retriever. However, there are few genetic mutations that can be used to describe and differentiate canine B cell lymphoma subtypes. To find an alternative solution, AKC Canine Health Foundation (CHF) funded investigators at the University of Missouri, Columbia examined the epigenetic characteristics of canine B cell lymphoma to see if they could identify any distinguishing features useful for diagnosing, treating, and providing a prognosis for affected dogs. (CHF Grant 01918-G: Discovery of Biomarkers to Detect Lymphoma Risk, Classify for Treatment, and Predict Outcome in Golden Retrievers) They focused on Golden Retrievers living in the United States because lymphoma is common in this breed and to study a genetically similar population of dogs. Their results were recently published in the peer-reviewed journal Epigenetics.1

What is epigenetics?

Epigenetics is the study of factors that alter gene function without changing the actual DNA sequence. One example of an epigenetic change is the chemical reaction known as methylation – or adding a methyl group to DNA, proteins, or other molecules. Methylation can turn genes on or off and even affect the risk of developing cancer.

In humans, increased methylation of various genes can be used to differentiate B cell lymphoma subtypes. In contrast, investigators were not able to find significant differences in the methylation pattern between canine B cell lymphoma subtypes in the population of Golden Retrievers studied. However, cancerous canine B cells did show a distinct increase in overall methylation compared to normal canine B cells. The pattern was similar to results previously reported in other breeds and other geographical regions (Europe). This finding suggests that the increased methylation pattern occurs in all dogs with aggressive B cell lymphoma, making the disease consistent across dogs with different genetic backgrounds and living in different geographic regions.

What does it mean?
Aggressive canine B cell lymphoma had a distinct pattern of increased methylation throughout the genome of the Golden Retrievers studied. While the methylation pattern could not distinguish various B cell lymphoma subtypes, the fact that increased methylation was so prominent suggests that this epigenetic change plays a key role in cancer development. A low degree of abnormal methylation was also found in some of the normal dogs studied, meaning those dogs could be at risk of developing lymphoma in the future.

The genes and biochemical pathways that consistently showed increased methylation in dogs with aggressive canine B cell lymphoma can potentially be used as biomarkers. Measuring them may help with diagnosis, prognosis, and understanding an individual dog’s risk of developing lymphoma. They could also be studied as treatment targets – if we can alter methylation, we may be able to disrupt the development of cancer. Future studies will explore how these epigenetic changes drive cancer development and continue to define canine lymphoma subtypes for better diagnosis, treatment, and prevention of canine B cell lymphoma. Learn more about CHF-funded lymphoma research at akcchf.org/lymphomaRPA.

  1. Chu, S., Avery, A., Yoshimoto, J., & Bryan, J. N. (2022). Genome wide exploration of the methylome in aggressive B-cell lymphoma in Golden Retrievers reveals a conserved hypermethylome. Epigenetics, 0(0), 1–17. https://doi.org/10.1080/15592294.2022.2105033

 

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