Study offers insight into
possible cause of lymphoma
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 reported Feb. 13 in Nature.
“The implications of these findings are considerable,” says 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 says, present a major risk to
Interestingly, these same repair enzymes recognize mutations in many other
types of genes in the B cells, but they fix those 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 showed 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 says.
“Most of these non-antibody genes do not accumulate mutations because the
repair, for whatever reason, is precise, not sloppy.”
What this means, Schatz says, 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 says. “We hypothesize that exactly
this sort of breakdown of the repair processes occurs in the early stages of
the development of B cell tumors.”
— By Jacqueline Weaver
T H I SW E E K ' SS T O R I E S
Yale-engineered virus can attack brain tumors
Trustees set next steps in residential college expansion
Going back to the ‘basics’ of medicine on the wards of Uganda
New center promotes the study of Hellenic culture and civilization
Study to examine Internet-based programs for diabetic children
Study offers insight into possible cause of lymphoma
Lorimer lauded for contributions to corporate boards
Yale chemist honored for contributions to teaching . . .
Show documents people and fauna of the ‘New World’
‘Chronicler of American life’ is next Maynard Mack lecturer
Contemporary images of the Virgin Mary are featured in . . .
Symposium will explore human rights issues related to . . .
Police Academy for citizens to be held this spring
Arabic music past and present is explored in new exhibition
Chinese ‘Year of the Rat’ celebrated at Yale
Hundreds of schoolchildren will gather in Yale ‘castle’ . . .
Yale Books in Brief
Bulletin Home|Visiting on Campus|Calendar of Events|In the News
Bulletin Board|Classified Ads|Search Archives|Deadlines
Bulletin Staff|Public Affairs|News Releases|
E-Mail Us|Yale Home