Colossal genome studies reveal breast cancer's complexity, Alzheimer's risks

This week, scientists unveil the genomes of tumors from 50 breast cancer patients and 5 new genes for Alzheimer’s from studies of over 50,000 people – each the largest studies of their kind, ever.

There’re good news and bad news.

1. The deeper researchers dive into the genetics of breast cancer, the more complicated their discoveries. And the latest, and deepest, dive is no exception, Nature reports.

A team led by Matthew Ellis at Washington University embarked on the single largest cancer genomics investigation to date.

“At least we’re reaching the limits of the complexity of the problem,” he says. “It’s not like looking into a telescope and wondering how far the universe goes. Ultimately, the universe of breast cancer is restricted by the size of the human genome.”

They sequenced the whole genomes of 50 breast cancer patients' tumors alongside matching DNA from the same patients' healthy cells in order to identify genomic alterations present only in the cancerous cells.

The cancers' genetic fingerprints are highly diverse. Of the 1,700 gene mutations they found in total, most were unique to individual patients' tumors, and only 3 occurred in 10% or more.

"The results are complex and somewhat alarming, because the problem does make you sit down and rethink what breast cancer is," says Ellis.

All told, about half the cancers carried a combination of 3 mutations – on MAP3K1, PIK3CA, and TP53 – leaving half with cancers arising from varying constellations of much rarer mutations.

“We get good therapeutic ideas from the genomic information,” Ellis adds. “The near-term goal is to use information on whole genome sequencing to guide a personalized approach to the patient’s treatment.” No single blockbuster drug will answer the problem.

Their findings were presented this weekend at the American Association for Cancer Research annual meeting in Orlando.

2. In two new studies that analyzed the genes of more than 50,000 people, scientists report new genes linked to the neurodegenerative Alzheimer’s.

In these genome-wide association studies (GWAS), researchers compared DNA extracted from tissue samples of Alzheimer’s patients with those of healthy people of the same age – looking for genes that popped up more frequently in the DNA of Alzheimer’s patients.

University of Pennsylvania’s Gerard Schellenberg and colleagues report the largest ever GWAS conducted in Alzheimer’s research. While Cardiff University’s Julie Williams and team conducted multi-stage follow-up to multiple previously reported GWAS.

Together, the studies report 5 more genes – ABCA7, MS4A4/MS4A6E, CD2AP, CD33, and EPHA1 – linked to Alzheimer's, bringing the grand total to 10 genes confirmed for susceptibility to the disease.

As the New York Times explains, by themselves, the genes are not nearly as important a factor as APOE, a gene discovered in 1995 that greatly increases risk for the disease (by 400% if a person inherits a copy from one parent, by 1,000% if from both parents).

In contrast, each of the new genes increases risk by no more than 15%, which means that they won’t be used to decide if a person is likely to develop Alzheimer’s. Their worth is in suggesting new areas of study that may help speed creation of therapies.

But if the effects of all 10 could be eliminated the risk of developing the disease would be cut by 60%.

Now the two teams are pooling their data to do an enormous study. “We are upping the sample size,” Schellenberg says. “We are pretty sure more stuff will pop out.” However, the teams warn that new treatments could be 15 years away.

Both studies were published in Nature Genetics this week.

Image: a visual representation of genomic disruptions in breast cancer / Matthew Ellis

This post was originally published on Smartplanet.com