Lymphoma Causes Are Now Better Understood

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Main Category: Lymphoma / Leukemia
Also Included In: Cancer / Oncology;  Immune System / Vaccines
Article Date: 18 Feb 2008 - 0:00 PDT

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According to a report this week in Nature, the cellular mutation and repair processes of the immune system provide information on the development of lymphatic cancer.

David Schatz, senior author of the study and immunobiologist at Yale School of Medicine, reports that "the implications of these findings are considerable." Widespread mutations and an increased risk of cancer could be the results of "anything that compromises the function of these DNA repair processes."

Lymphatic cancer, or lymphoma, is a type of cancer that originates when a type of white blood cell (lymphocyte) becomes abnormal or mutated. One piece of the lymphatic system is infection-fighting lymphocytes called B cells. The researchers focused on the somatic hypermutation (SHM) process, which introduces random mutations in B cells' antibody genes to make them more effective in fighting infection.

There are two steps in the SHM process:

1. A mutation initiator - or activation-induced deaminase (AID) - causes genetic mutations.
2. DNA repair enzymes spot the changes and begin making "sloppy" repairs, leading to even more mutations.

When these two steps combine, they present a major risk to genomic stability - the ability of DNA to perform its duties of replication, recombination, and repair without mutation. The same DNA repair enzymes are able to see mutations in many other types of genes present in the B cells, but they fix the genes in a very precise manner.

Previously, researchers believed that genomic instability was not likely since the first step of the SHM process only happened in antibody genes. However, Schatz and colleagues discovered that AID acts on many other genes in B cells, including genes linked to lymphatic and other types of cancer.

Schatz indicated that the research team was surprised when learning that, "most of these non-antibody genes do not accumulate mutations because the repair, for whatever reason, is precise, not sloppy." This means that researchers who study lymphatic cancer must understand both the original mutations and the repair process.

"If the precise, or high fidelity, repair processes break down, this would unleash the full mutagenic potential of the initial mutation, resulting in changes in many important genes," Schatz reports. "We hypothesize that exactly this sort of breakdown of the repair processes occurs in the early stages of the development of B cell tumors."

Nature: doi:10.1038
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Written by: Peter M Crosta
Copyright: Medical News Today
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