New study offers insight into possible cause of lymphoma

Feb 14, 2008

The immune system's powerful cellular mutation and repair processes appear to offer important clues as to how lymphatic cancer develops, Yale School of Medicine researchers report this week in Nature.

"The implications of these findings are considerable," said David Schatz, a Howard Hughes Medical Institute investigator, professor of immunobiology at Yale, and senior author of the study. "It now seems likely that anything that compromises the function of these DNA repair processes could lead to widespread mutations and an increased risk of cancer."

The lymph system is made up of infection-fighting B cells. Schatz and his colleagues examined the somatic hypermutation (SHM) process, which introduces random mutations in B cells' antibody genes to make them more effective in fighting infection.

SHM occurs in two steps: First, a mutation initiator, or activation-induced deaminase (AID), causes genetic mutations. Second, DNA repair enzymes spot the changes and begin making "sloppy" repairs, which lead to yet more mutations. The two steps combined, Schatz said, present a major risk to genomic stability.

Interestingly, these same repair enzymes recognize mutations in many other types of genes in the B cells, but they fix the genes in a precise, or, "high fidelity," manner.

Up until now it was thought the risk to genomic stability was avoided for the most part because the first step of the SHM process only happened in antibody genes. But this study found that AID acts on many other genes in B cells, including genes linked to lymphatic cancer and other malignancies.

"And then we had another surprise," Schatz said. "Most of these non-antibody genes do not accumulate mutations because the repair, for whatever reason, is precise, not sloppy."

What this means, Schatz said, is that researchers studying lymphatic cancer must understand both the first and the second step-the original mutations and then 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 said. "We hypothesize that exactly this sort of breakdown of the repair processes occurs in the early stages of the development of B cell tumors."

Citation: Nature: doi:10.1038

Source: Yale University

Explore further: Multiphoton microscopy reveals features of basal cell carcinoma

Related Stories

High fidelity: Researcher finds keys to genome integrity

Apr 14, 2015

Maintaining the stability and the correct sequence of our genetic information is vital to the accurate transmission of our genetic code. However, in the course of replicating, our DNA frequently runs into ...

Researchers clarify how DNA damage signaling works

Mar 31, 2015

The DNA molecule is chemically unstable, giving rise to DNA lesions of various kinds. That is why DNA damage detection, signaling and repair, collectively known as the DNA damage response, are needed. The ...

Recommended for you

What's the harm in alternative therapies?

2 hours ago

We often see stories in the media about cancer patients who have chosen alternative treatments, either alongside or instead of conventional treatment.

'Chemo brain' is real, say researchers

Apr 27, 2015

UBC research shows that chemotherapy can lead to excessive mind wandering and an inability to concentrate. Dubbed 'chemo-brain,' the negative cognitive effects of the cancer treatment have long been suspected, ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.