Meningioma: What Do Genes Have To Do With It

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Meningioma What Do Genes Have To Do With It?
Mark D. Johnson, M.D., Ph.D. Department of
Neurosurgery Brigham and Womens Hospital/Harvard
Medical School
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The Human Body Is Very Much Like A Bustling
Community
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Every cell and every protein within the cell has
a special role to play
Urban75.org
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Every cell and every protein within the cell has
a special role to play
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Every cell and every protein within the cell has
a special role to play
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Every cell and every protein within the cell has
a special role to play
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Every cell and every protein within the cell has
a special role to play
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Although some cells and proteins have functions
that no one understands
Hulk Hogan - WWF
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Genes Are DNA Messages That Contain the
information Needed To Make Proteins
Mother Father
Messenger RNA
2 Working Copies of Each Gene (Normal)
Protein
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Some genes determine whether new cells are born
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Some genes determine whether new cells are born
Some genes make cells grow
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Some genes determine whether new cells are born
Some genes make cells grow
Some genes make cells stop growing
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Some genes determine whether new cells are born
Some genes make cells grow
Some genes make cells stop growing
Some genes make cells die
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Sometimes, genes that normally serve a useful
function undergo a change
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and start to make trouble. This can cause
cells to grow abnormally and form Tumors
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Thats why every cell needs law enforcement genes
to SUPPRESS TUMOR GROWTH
Courtesy of Barneyfife.com
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Knudsons Two Hit Hypothesis for Tumor Suppressor
Genes
DNA Replication
2 Working Copies of Gene (Normal)
1 Working Copy of Gene (Susceptible)
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One Copy of the Gene May Produce a Marginal
Amount of Tumor Suppressor Protein, and This Can
Increase the Risk for Tumor Formation
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What If You Lose Both Copies of A Tumor
Suppressor Gene?
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Without the Tumor Suppressor Proteins Around,
Things Can Get Out of Hand
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And before you know it, youve got a monster
(i.e. tumor) on your hands!
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NF2 (neurofibromatosis type II) is a tumor
suppressor gene that is mutated in half of all
meningiomas
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Cells will travel around and divide to reproduce
themselves when there are too few of them
Courtesy Nikon Microscopy U
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NF2 protein tells cells to stop traveling and
stop dividing when there are enough cells
Nikon Microscopy U
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Loss of the NF2 protein allows cells to keep
traveling and keep dividing, similar to the
behavior of the fibroblasts shown in the video
below
Nikon Microscopy U
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Without NF2, the cells dont get the proper
signal to stop growing and traveling when there
are enough cells
Lallemand et al, 2003
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Growth Factor Receptors
Adhesion Receptors
p120RasGAP NF1 (neurofibromin)
Rho
cytoskeleton
Ras
Migration
Raf
Rac
cytoskeleton
PI3 kinase
MEK
Akt
ERK
NF2 (merlin)
MAP kinase
PAK
nucleus
Proliferation
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Most meningiomas arise from the coverings of the
brain
top
top
ear
forehead
back
Frank H. Willard, Ph.D., 2000
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They are thought to arise from the arachnoid, but
are often stuck to the dura
Frank H. Willard, Ph.D., 2000
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Presumably, it Is loss of NF2 gene function in
one of these cells
Normal Arachnoid
Normal Arachnoid Villi
Meningioma
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that leads to meningioma formation in about half
of all cases.
top
meningioma
front
back
http//www-medlib.med.utah.edu
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The fact that only half of meningiomas have a
loss of NF2 suggests that Other Tumor Suppressor
Genes may be lost
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or Growth-stimulating Genes may be gained and
out of control in meningiomas
DC Comics
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Some of these changes have been identified, and
likely contribute to meningioma progression
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Many more of these genes still need to be
identified.
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You, the Brigham and the Brain Science Foundation
Are working together in the fight to understand
and cure Meningioma