MARGINALIA
By Any Other Name
By giving tumors their right names, scientists gain power over them
Robert L. Dorit
Molecular Choir
In the end, our ability to name diseases properly may depend on our
getting to know them better, or on looking beneath surface
appearances for deeper understanding. Virtually every human cell
carries within it the entire human genome, 30,000 different
instructions for the manufacture of 100,000 proteins. At any point
in space and time, some instructions must be sung out loud, others
left silent. The identity, location and function of every cell in
our body depend on the correct interpretation and interplay of those
musical fragments. At this scale, healthy cell behavior depends on a
well-rehearsed and synchronized molecular chorus. Conversely, every
genetic disease reflects a rogue element in the choir, a disturbance
in the careful interpretation of biological information. Cancer is
no exception.
We have known for a century that cancer must involve a deep
disturbance in the mechanisms that regulate cell growth, cell
division and cell identity. But until recently, we were not in a
position to ask intimate questions of the 30,000 molecular singers
on the cellular stage: Who is singing off-key? Who is coming in too
soon or too late? Now, thanks to technology developed in conjunction
with the Human Genome Project, we can look at what each gene is
doing in the cell at any point in time. More precisely, we can look
at how loudly each of the 30,000 genetic instructions is being sung
at any point in time. With this technology, we can also ask the
question we have been hinting at from the outset: Are all breast
cancers the same and hence deserving of the same name?
At the genomic scale, every breast cancer examined shows a large
subset of genes being read differently than they would be in normal
breast cells. Some genes are read too loudly
("overexpressed"), others too quietly
("underexpressed"), and it is the noise of these
undisciplined molecular voices that results in breast tumors. But
are all breast tumors reading the same, albeit incorrect, score? The
answer is an unequivocal no, which perhaps should not surprise us. A
condition that is characterized by a malfunction of the delicate
processes that regulate cell growth and division is not likely to
result from the same, single cause in every case.
The tragic reality of our lives is that there will always be many
more ways of screwing things up than there will be of getting them
right, and this axiom holds true of biological systems as well.
Breast cancer turns out to be a heterogeneous collection of
molecular miscues. Hidden beneath the apparent similarity of all
breast cancers lie many corrupt musical scores. What once seemed to
us a single illness with a similar set of underlying causes has been
transformed into multiple discordant conditions. Choruses of genes
that carry the tune in normal cells blare in certain breast tumors
but only whisper in others. What seemed simple suddenly appears
hopelessly complicated.
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