Decoding Cancer

The first map of breast-tumor genomes could revolutionize patient care

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Treating cancer is a bit like shooting in the dark. Sometimes it works. Sometimes it doesn't. There's no way to predict. That's because while scientists have some crude ideas about how to disable cancer cells, the inner workings of cancer are a mystery for the most part.

Perhaps not for long. Researchers have just sequenced the entire DNA code of one type of breast-cancer tumor. The team, led by scientists at Washington University School of Medicine, began the project using tumor samples from 50 women enrolled in another of their studies. All the women had breast tumors that contained estrogen receptors, but only about half the patients had responded to drugs that targeted the receptors. To figure out why, the researchers sequenced the whole genomes of the breast cancers of all 50 women.

The genetic maps provided some intriguing clues: the patients' tumors harbored more than 1,700 genetic mutations, most of which were unique to the women in whom they originated. Of the few gene mutations shared by many of the women, some were familiar--previously associated with cancer in other studies--and some were completely new. Those aberrations could help explain why the women responded differently to the drugs. And although the sheer number of genetic abnormalities suggests that cancer may vary from one person to the next, most of the changes actually fed into common pathways of tumor development. These, say the authors, could become targets of broadly useful new drugs. Indeed, there are already drugs on the market that address six of the mutations, and doctors are eager to test their effectiveness against breast cancer.

A similar genetic dossier from dozens of tumors exists for one other cancer, multiple myeloma. Together, these sets of genomes represent a new era in cancer treatment, in which doctors may finally be able to match each patient to the best possible treatment.

ALZHEIMER'S

Scientists Identify Five New Genes

In a genetic analysis of more than 50,000 people, researchers have discovered five new genes that raise the risk of late-onset Alzheimer's disease. The additions, which bring the total number of known risk genes to 10, are associated with the disorder's most common form, which affects up to 50% of people over age 80.

Experts are excited because the newly revealed genes involve things that scientists have long suspected of playing a role in Alzheimer's but have never been able to confirm: high cholesterol, inflammation and the way cells ferry molecules around. Already existing genetic risk factors are generally related to the formation and accumulation in the brain of the disease's hallmark amyloid plaques.

The new genes together may account for only about 35% of late-onset Alzheimer's cases, but the novel processes they implicate could provide fresh targets for better drugs. Currently, the best medications can only alleviate, not prevent, the main symptom, memory loss. It's a long way from genes to therapy, but the new discoveries are an important step in that direction.

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