Putting the human genome to work — on cancer
By Robert Levy
Imagine studying history without a map of the world. Then imagine studying history with only a map of the world.
The names and locations of countries would be clear, but what else? A map alone can't show which countries are allies and which are enemies, which are peaceful and which are aggressors, which have similar exports, or which are the most powerful. Neighbors aren't always amicable, and size says nothing about influence.
An illustration of DNA
So it was, at first, with the map produced by the Human Genome Project — the recently completed guide to the "home addresses" of the 30,000-odd genes located on the chromosomes of human cells. Knowing a gene's region and assigning it a name (usually something coded and curt like VDAC2 or INK4a, but occasionally whimsical like hedgehog) reveals little of what scientists ultimately wish to know: What precisely does a particular gene do? Which genes cooperate with it, and which hinder it? Which switch it on and off? What happens when it goes awry?
If sequencing the genome isn't sufficient for answering these questions, it is indispensable to approaching them. The map has become the essential reference guide — the inventory par excellence of the working parts of the genetic code — for scientists exploring the roots of human illness. This is nowhere more evident than in the study of cancer, which is, for all its multiplicity of forms, fundamentally a disease of abnormal or malfunctioning genes.
The most familiar outgrowth of the genome project is gene-expression profiling, sometimes known as microarray or "gene chip" technology. The process enables researchers to sample the activity of thousands of genes at a time, producing a grid-like pattern that serves as the molecular calling card of individual tumors. Pioneered at Dana-Farber and other research centers, the technique makes it possible to draw finer distinctions between tumors, leading to more precise diagnoses and, potentially, more accurately targeted therapies.
But expression profiling is far from the only way the genome is being put to work, and expression profiles themselves are not as cut-and-dried as they may seem at first. In many cases, they open up as many questions as they answer. Several Dana-Farber scientists are using the genome map to extend and, in fact, transcend microarray technology. Here is a brief look at three of them.
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