Good Morning All,
Thought this might be of some use to you as well.
Mutations not the only gene defect that leads to cancer
COLUMBUS, Ohio -- New research shows that gene mutations are not the
only
kinds of defects involved in the transformation of a healthy cell into a
malignant one. Scientists say that this may mean the nature of cancer is
even more complicated than once thought.
Another kind of defect, one that turns off genes without changing their
DNA,
is also at work, and probably to a much greater degree than ever
suspected.
The findings, published recently in the journal Nature Genetics,
strongly
suggest that an unknown number of genes -- over and above those affected
by
mutations -- are involved in the cancer process.
"Science has been studying changes and alterations at the genetic level
in
cancer cells, and we thought we understood tumor progression," said
Christoph Plass, assistant professor of molecular virology, immunology,
and
molecular genetics at the Ohio State University Comprehensive Cancer
Center.
"Now there is this second layer of complexity. A lot of scientists are
going
to be kept very busy trying to understand this," said Plass, coordinator
and
one of the principal investigators of the study.
This type of gene defect involves a process known as DNA methylation.
Normally, healthy cells use DNA methylation during development and
throughout life to turn off genes that are not needed. In cancer cells,
aberrant DNA methylation turns off genes that would normally prevent
inappropriate cell division. In other words, it shuts down one of the
body's
best mechanisms that prevents a cell from becoming cancerous.
"This is the first time in which DNA methylation has been studied in
human
cancer on a scale this large and in which different tumor types have
been
compared."
The research presented several surprises.
"When we began this study, we expected to find methylation in a few key
tumor suppressor genes," he said. "Nobody expected to find this high
degree
of methylation."
In fact, the researchers found that up to 10 percent of the genes in
some
tumors types were inactivated by methylation.
"This was surprising because it suggests that 4,000 to 5,000 genes might
be
deregulated (turned off) by aberrant DNA methylation in some types of
tumors."
There were other surprises as well.
DNA methylation in cancer was discovered about 10 years ago and until
now,
people believed that its role in cancer was limited to inactivating
tumor-suppressor genes.
"We were surprised to find that only 40 percent of the methylation
events we
detected involved changes in gene activation, while the other 60 percent
did
not," said Plass. "The genes represented by this 40 percent should be
investigated for their relationship to cancer.
"The function of those genes whose activation remains unchanged by
methylation is unclear, though, as are the consequences of this
methylation
for the cell. We believe that methylation may contribute to the overall
genetic instability in the tumor." Genetic instability refers to the
ease
with which malignant cells can develop additional mutations.
The researchers also found that the pattern of methylation was very
specific
for some types of tumors.
"This aberrant methylation doesn't occur at random," he said. "In some
tumor
types -- leukemia and head and neck cancer, for example -- certain genes
are
methylated in very specific places, and we can use those sites as
markers
for certain tumor types."
Aberrant DNA methylation may therefore provide a way to identify
subtypes of
cancer that respond better to certain kinds of treatment.
Plass said there is also preliminary evidence suggesting that resistance
to
chemotherapy is in some cases linked to the degree of aberrant
methylation
in some tumors.
The study, conducted by Plass and a large team of researchers, examined
98
tumor samples to determine if any of the islands were methylated. The
samples came from seven types of tumors: breast, colon, glioma, head and
neck, leukemia, testicular, and primitive neuroectodermal tumors of
childhood (PNET).
How DNA methylation turns off genes, and why it goes wrong in cancer
cells
is still unknown.
###
Contact: Christoph Plass, (614) 292-6505;
Plass-1@medctr.osu.edu
Written by Darrell E. Ward, (614) 292-8456;
Ward.25@osu.edu
God Bless You All,
marty auslander
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