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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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