Feb. 1, 2007 -- Genetic fingerprints that reveal where
a brain cell came from remain distinct even after the
cell becomes a brain tumor, an international coalition
of scientists will report in the February 1 issue of
finding adds a new layer of complexity to the quest
to understand the causes of childhood brain cancers,
according to senior author David H. Gutmann, M.D., Ph.D.,
the Donald O. Schnuck Family Professor of Neurology
at Washington University School of Medicine in St. Louis
and co-director of the neuro-oncology program at the
Siteman Cancer Center. "Our findings suggest
that brain tumors arising in different regions may be
genetically distinct as a consequence of their unique
cellular origins," Gutmann says. "This is
yet another factor we need to consider when trying to
understand how pediatric brain tumors form."
use information about tumor origins to develop new tests
and treatments for the tumors. Brain tumors are the
leading cause of cancer-related death in children, and
the most common childhood brain tumor is the pilocytic
astrocytoma (PA). Approximately 15 percent of all PAs
are linked to neurofibromatosis 1 (NF1), a genetic condition
that causes childhood brain tumors and is a primary
focus of Gutmann's research. However, the genetic basis
for the majority of PAs is unexplained.
the new study, Gutmann led six laboratories in the most
detailed genetic analysis of PAs to date. "We
were hoping to identify genes that contribute to the
formation of these tumors and find indicators that might
help us predict which tumors will be relatively well-behaved
and which will be more aggressive," Gutmann says.
studies have failed to produce any solid leads on the
genetic alterations that predispose children to PAs.
"It should be recognized that the genetic
alterations in this tumor may be very subtle,"
Gutmann notes. "When we looked at gene activity
levels in the tumors as a function of brain location,
though, a very interesting pattern began to emerge."
in different parts of the brain carry the same genes,
but they also contain factors that modify the use of
those genes, suppressing some genes and activating others
to allow the cells to take on specialized characteristics
as the brain matures. These changes in gene activity
levels are called changes in gene expression.
The researchers found that tumors arising in different
regions of the brain retain distinct patterns of gene
expression. These patterns provided genetic fingerprints
or bar codes for the location of PAs, as well as for
another glial cell tumor called an ependymoma. In addition,
scientists also detected these distinct patterns of
expression in normal glia and stem cells from these
brain locations, suggesting that genetic fingerprints
can be used to identify the potential origins of brain
tumors. "There's been a movement in recent
years to link normal brain development to pediatric
neuro-oncology, and these findings affirm that as a
necessary approach," Gutmann says. "We won't
fully understand the causes of pediatric brain tumors
until we consider them in the context of factors that
shape the development and specialization of different
MK, Mansur DB, Reifenberger G, Perry A, Leonard JR,
Aldape KD, Albin MG, Emnett RJ, Loeser S, Watson MA,
Nagarajan R, Gutmann DH. Distinct genetic signatures
among pilocytic astrocytomas relate to their brain region
origin. Cancer Research, February 1, 2007.