Brain tumor 311.
(photo credit: courtesy Mayo Foundation)
Scientists showed in mice that disabling a gene linked to a common
pediatric tumor disorder, neurofibromatosis type 1 (NF1), made stem
cells from one part of the brain proliferate rapidly. But the same
genetic deficit had no effect on stem cells from another brain region.
results can be explained by differences in the way stem cells from
these regions of the brain respond to cancer-causing genetic changes.
is among the world’s most common genetic disorders, occurring in about
one of every 3,000 births. It causes a wide range of symptoms, including
brain tumors, learning disabilities and attention deficits.
tumors in children with NF1 typically arise in the optic nerve and do
not necessarily require treatment. If optic gliomas keep growing,
though, they can threaten the child’s vision. By learning more about the
many factors that contribute to NF1 tumor formation, scientists hope to
develop more effective treatments.
“To improve therapy, we need
to develop better ways to identify and group tumors based not just on
the way they look under the microscope, but also on innate properties of
their stem cell progenitors,” says David H. Gutmann, MD, PhD, the
Donald O. Schnuck Family Professor of Neurology.
The study appeared recently in Cancer Cell
. Gutmann is also the director of the Washington University Neurofibromatosis Center.
the new study, researchers compared brain stem cells from two primary
sources: the third ventricle, located in the midbrain, and the nearby
lateral ventricles. Before birth and for a time afterward, both of these
areas in the brain are lined with growing stem cells.
author Da Yong Lee, PhD, a postdoctoral research associate, showed that
the cells lining both ventricles are true stem cells capable of becoming
nerve and support cells (glia) in the brain. Next, she conducted a
detailed analysis of gene expression in both stem cell types.
are night-and-day differences between these two groups of stem cells,”
Gutmann says. “These results show that stem cells are not the same
everywhere in the brain, which has real consequences for human
The third ventricle is close to the optic
chiasm, the point where the optic nerves cross and optic gliomas develop
in NF1 patients. Lee and Gutmann postulated that stem cells from this
ventricle might be the source of progenitor cells that can become
gliomas in children with NF1.
To test the theory, they disabled
the Nf1 gene in neural stem cells from the third and lateral ventricles
in the mice. This same gene is mutated in patients with NF1, increasing
their risk of developing tumors.
Lee found that loss of Nf1
activity had little effect on stem cells from the lateral ventricle, but
stem cells from the third ventricle began to divide rapidly, a change
that puts them closer to becoming tumors.
The third ventricle
usually stops supplying stem cells to the brain shortly after birth.
When researchers inactivated the Nf1 gene before the third ventricle
closed, the mice developed optic gliomas. When they waited until the
third ventricle had closed to inactivate the Nf1 gene, gliomas did not
Gutmann plans further studies to determine whether all
NF1-related optic gliomas form in cells descended from the third
ventricle. He suspects that additional factors are necessary for optic
gliomas to form in cooperation with Nf1 gene loss in third-ventricle
“We have to recognize that cancers which appear very
similar actually represent a collection of quite different diseases,” he
says. “Tumors are like us — they’re defined by where they live, what
their families are like, the traumas they experience growing up, and a
variety of other factors. If we can better understand the interplay of
these factors, we’ll be able to develop treatments that are much more
likely to succeed, because they’ll target what is unique about a
specific patient’s tumor.”
Washington University School of
Medicine’s 2,100 employed and volunteer faculty physicians also are the
medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The
School of Medicine is one of the leading medical research, teaching and
patient care institutions in the nation, currently ranked sixth in the
nation by US News & World Report. Through its affiliations with
Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine
is linked to BJC HealthCare.This article was first published at www.newswise.com