I would like to outline some of the recent research
into the causes of lipomatosis. The revolution in genetic research
has enabled big advances in the understanding of tumors over the last
few years. Although this work has NOT identified any easy cures or
treatments, it at least points us in the right direction. Below is
my overview. I'll use the term generic term "lipoma" but my
perspective is FML. I am not sure to what extent this applies to
other lipoma types such as Dercum's.
THE CAUSE OF LIPOMATOSIS
WHAT IS LIPOMA: Every cell contains very complex biochemical
controls that tell it when it should divide and when it should not
divide. The "blueprint" for this mechanism is encoded in each cell's
DNA, which dictates which proteins are produced and when. When this
cell-division control mechanism does not function properly, cells
continue to divide uncontrollably. This is the definition of a
tumor. If the tumor is of the type in which the damaged DNA is able
to spread throughout the body (e.g.—"metastasize") then this tumor is
classified as a "cancer". Tumors that do not spread to other,
healthy tissues are called "benign tumors". Lipoma is a benign
WHAT CAUSES TUMORS: There are many ways in which the cell's growth-
control machinery can become damaged in a way that causes tumors.
For example, some tumors are caused when a virus alters the DNA.
Some environmental factors can also damage healthy DNA. However, in
the case of most lipomatosis, the cause is a translocation mutation.
Translocation mutations are not caused by environmental factors and
they don't happen after someone is born.
HOW A TRANSLOCATION MUTATION OCCURS: Each cell except for sperm and
egg has 46 chromosomes. Sperm and egg each have 23 chromosomes, so
that a combination of a sperm and an egg results in the correct
number of 46. In order for the body to create an egg or sperm it
must break a 46-chromosome cell down into two 23-chromosome cells.
This requires a physical ripping apart of the chromosome pairs.
Sometimes this process goes awry and chromosomes break. The egg or
sperm with a broken chromosome is unable to conceive. Sometimes a
part of the chromosome breaks off but then reattaches itself just as
good as new. But there is a third possibility, and herein lies our
Sometimes two chromosomes break at the same time. Then, instead of
the broken off pieces reattaching themselves to the chromosome from
which they came, they switch spots. This creates two "repaired"
chromosomes, but a piece of them has been switched. This is called
a "balanced reciprocal translocation". Breakages in chromosomes
occur most frequently at the normal weak points in the physical
chromosome structure. One of these weak points is on chromosome 12,
near the halfway point of the large or "q" half. Guess which gene
happens to reside at that weak point? A key gene that codes some of
the signaling proteins that play a key role in regulating cell
Unlike many mutations, the egg or sperm with a translocation mutation
is viable for conception. So the baby is born. The mutation does
not prevent birth because the genes that have been "translocated" to
an incorrect chromosome can, for the most part, still perform their
function. These genes are not missing (as in a "deletion mutation"),
they are just located on the wrong chromosome.
If someone with this mutation has a cytogenetic analysis run on
themselves, the lab can easily see that some of the genetic material
that should be on chromosome 12 is located on a different chromosome
(usually 13). Some researchers have published the relationship
between different specific mutations and the specific associated
types of lipomas. Also, fusion of that common break point on 12
with some genes will cause disorders more serious then lipoma. For
example, if a specific portion of 15 is the translocation
counterpart, then the person will suffer not from lipoma but from
WHEN DID THE MUTATION OCCUR: This mutation during the formation of
sperm or egg may not have occurred in the immediate parents of the
lipoma patient. It may have occurred a thousand years ago, in one of
their ancestors. Since it is a "dominant" trait, pairing with it a
non-mutant gene from an unaffected mate does not prevent the
formation of the tumors.
CLINICAL MANIFESTATION: A person can live for years without
suffering from any adverse effect from this mutation. Imagine a
quarterback that is great at running-plays and short passes, but bad
at long passes. He looks fine until his team gets behind and they
really need to throw long bombs. Then the quarterback starts to
throw interceptions and can't do his job. Another analogy: the
quarterback works great with his favorite receiver John, but always
misses when he tries to throw to the other receiver Joe. This is
isn't Joe's fault--John and Joe are equally good receivers. The
quarterback looked great when John was in the game, but as soon as
the coach put Joe in the game, the quarterback couldn't do his job.
In reality, the quarterback brought his weakness into the game from
the start, but it only became apparent later, due to interactive
factors (when he had to start throwing to Joe).
At some point, in some cells, the translocated genes can no longer do
their job while being located on the wrong chromosome. The "on-off
switch" in the cell division machinery in this cell gets stuck on
the "on" setting. The cells continue to divide. All the daughter
cells of this cell also continue to divide. This creates a mass of
tissue, in which all cells are continuing to divide when they
shouldn't be dividing. This is a lipoma tumor.
IMPLICATION FOR TREATMENTS: So what do we know about how to fix
this? Well, unfortunately that gene that got shifted to the new
location does not act alone in controlling fat cell division. It's
just one player on a big team. And we don't even know the plays or
who the other players are. We don't know exactly how this gene
interacts with others to encode proteins that regulate cell growth.
So we don't know that the quarterback is able to throw to John but
not to Joe. We don't even know that John or Joe (other genes in the
DNA code) are in this game. So all we can say is: this quarterback
has a problem in which sometimes he can be successful and other times
Hopefully, this background can help you better understand some
aspects of lipomatosis. For example, some people ask: "If my lipoma
is due to a mutation that I was born with, then why didn't I start
getting any tumors until I was 20--—the same year in which I started
to drink a lot of coffee?" Hopefully the explanation above might
help people understand that a mutation can exist for years without
manifesting any problem. Yes, you may have started to see lipomas at
the same time as you started to drink coffee. You also hear a
rooster crow before you see the sun rise, but you recognize that this
doesn't prove that the rooster is causing the sun to rise.
Another implication is that some of the justifications for some of
the homeopathic treatments are obviously invalid. For example, one
treatment is supposed to eliminate lipomas by "cleansing the body of
toxins". Anyone who understands the real cause of lipomatosis would
recognize that the problem is not due to "toxins" that can
be "cleansed". This "toxic cleansing treatment" is a scam that preys
on uninformed patients.
Let me offer one last example of how understanding these mechanisms
can help a lipomatosis patient. Some uninformed patients fear that
their lipoma might somehow "turn to cancer". Well….most lipomas are
12q13-15 reciprocating with 13q12-14. (Other lipomas involve 6p and
13q.) In most lipomsarcoma the 12q rearranges and fuses with the
16p. So if a person was born with a 12 to 13 mutation, why should he
fear that he would somehow contract a disease that results from a 12
to 16 mutation? Do you see how powerful it is to understand the real
cause of lipomatosis?
HOW THIS EXPLAINS CLINICAL VARIATION: My siblings have five lipomas
each, while I have had 130 appear. I mentioned in my previous post #
1542 that longitudinal studies have found no observable cause for
this variation in expression of the mutation. Coffee drinkers with
the mutation don't get more lipomas than non-coffee drinkers with the
mutation. These studies have ruled out all measurable environmental
factors, yet there are clearly different disease severities among
people with the same mutation. The reason is that, while my siblings
and I both have the same quarterback with the same problem (the
translocation mutation), my playbook is written to use Joe more than
my sibling's playbooks. So our shared inherent flaw in the
quarterback shows up more with me than my siblings. The hidden
factor that no one participating in a longitudinal study will ever
write in their diary is the interaction of the translocated genes
with other normal genes.
This also helps explain why the efforts of the misinformed people
posting to Dave's board are futile. People keep asking questions
such as: "Do all of us lift weights? Is that the cause of the
lipomas?" They are looking at visible factors (that would have shown
up in longitudinal studies decades ago) and are unaware of endogenous
invisible interactions between DNA segments.
TRANSMISSION OF THE MUTATION: Your 46 chromosomes are structured as
23 pairs of two. Let's say that your translocation is between
chromosomes 12 and 13. On these two chromosome pairs, you have one
unmutated chromosome and one mutated chromosome. So you have an
unmutated 12, a mutated 12, an unmutated 13 and a mutated 13. The
key gene that is supposed to be located on chromosome 12 is located
on chromosome 13 in your mutated 13, but on your unmutated 12 it
correctly resides on your 12.
Now it's your turn to produce egg or sperm. You will donate one
chromosome from each pair. There is an equal chance of it being your
good chromosome as your mutated chromosome. Any given egg or sperm
has an equal chance of getting any of the following combinations:
1. Good 12 and good 13—your child has no lipomas at all.
2. Mutated 12 and mutated 13--you successfully conceive but your
child has lipomatosis. The gene is supposed to be on chromosome 12
is on chromosome 13.
3. Mutated 12 and good 13—this is an "unbalanced translocation" It
doesn't work because now the combination is missing the gene that is
supposed to be on chromosome 12. This egg will either not conceive
or you (or your wife) will have a miscarriage before you are even
aware that you became pregnant.
4. Good 12 and mutated 13: Same. Unbalanced and not viable. You
have the key gene twice, once on the good 12 and once from the
IMPACT OF THIS TRANSMISSION MECHANISM: Your successful conceptions
will have a 50-50 chance of getting the mutation. I have one
brother who has no lipomas. He got the good chromosomes from both
pairs. He is not a "carrier". There is no such thing as a "carrier
for dominant traits. The mutation is completely gone from this
brother's line. Another implication is that someone with lipomatosis
may take longer to conceive.
Hopefully, this note will answer a variety of questions that lipoma
patients might have. Sorry for the length, but I thought that one
long post might cover a lot of questions that people have.
http://health.groups.yahoo.com/group/Li ... ssage/1571