News from the Front in War on Cancer--Mission Not Accomplished ...

Genetic sequencing has dumped a mountain of data into researchers' laps, but it hasn't yielded a silver bullet to cure cancer

By Marissa Fessenden

SEQUENCE: A DNA microarray Image: Public Domain image created by National Institutes of Health via Wikimedia Commons

Janet Rowley noticed something odd about the glowing chromosomes revealed by her microscope. It was the early 1970s, the first years of the so-called "war on cancer," and she was using a new staining technique to examine cells from patients with chronic myelogenous leukemia (CML), a cancer of the blood that was almost always fatal. The technique highlighted bands within the chromosomes, and she could see an extra piece on the end of chromosome 9. That fragment was nearly the same size as a "missing" chunk of chromosome 22 that other researchers had detected a decade earlier. To Rowley, it looked as if the tips of these two chromosomes had swapped places, or translocated. During the next few years she found two other cases of chromosomal translocation in different forms of leukemia. The finds forever changed the way scientists thought about cancer.

Shuffled chromosomes in leukemia established that broken, scrambled and messed-up genes cause cancer. The genetic code details when cells should grow, divide and eventually die. Cancer is a disease of misinformation?cells ignore the rules, growing despite multiple molecular signals telling them to stop and invading other tissues because they no longer respond to biological messages to stay put or even destroy themselves. In the past four decades scientists have identified thousands of genetic mistakes that either cause cancer or boost the risk of developing it. The effects of these typos are sometimes dramatic?the gene variants BRCA1 and BRCA2 can boost women's lifetime risk of developing breast cancer from 12 percent to 60 percent. Some errors are found only in cancer cells themselves; other changes can be passed from generation to generation. The latter are the mistakes that may be passed down and boost the risk of developing cancer?this is the inherited genetic risk, or the reason that people with a familial history of a disease may want to get tested earlier or more often.

As researchers uncover more genetic mistakes and delve deeper into the human genome, it may be possible to pin down the exact probabilities conferred by inherited genetic risk. If clinicians could scan a healthy person's genes for variations that explain their probability of developing cancer, perhaps they could prevent or catch the disease before it became a problem: Spit into this vial and the doctor will tell you what will ail you in 20 years.

Despite the plummeting cost of DNA sequencing technology, much of the information is a jumble of alphabet soup. Science can figure out what gene variants and markers a person has, but they can't tell exactly what it means for his or her health. It will take researchers years to untangle the genetics of cancer. Even large steps, heralded as a major advances, answer few questions and pose many more.

This spring, a massive international collaboration doubled the number of known genetic regions associated with the risk of breast, prostate or ovarian cancers. The genetic markers are signpost that researchers can follow to better understand the biology of these cancers. Only a few of the 74 newly identified markers are shared by more than one type of cancer, underscoring cancer's complexity. Yet exactly how the findings can inform public health recommendations remains to be discovered. Each marker is associated with small modifications of risk, but the effects add up. The findings could lead to more accurate cancer screening and hint at ways cancers could be caught before the disease becomes aggressive. Only further study, however, will show where to draw the lines between risk percentages that tell patients "not to worry" or "get tested now."

Source: http://www.scientificamerican.com/article.cfm?id=news-from-cancer-war

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