Understanding the genetic changes in tumors that distinguish the most lethal cancers from more benign ones could help doctors better treat patients.
Today, Swedish researchers are launching a new open-access catalog that maps many of those genetic changes. This “atlas” links thousands of specific genes involved in numerous cancers to patient survival and also reveals potential new drug targets.
The new atlas is one of several ongoing efforts to make sense of data that’s been collected by public databases—like the National Cancer Institute’s Cancer Genome Atlas—that act as repositories for tumor samples. The goal is to glean practical information, like markers of disease, that can be used to develop cancer drugs and diagnostics.
To generate the atlas, researchers led by Mathias Uhlén, a professor of microbiology at the Royal Institute of Technology in Sweden, used a supercomputer to analyze 17 major types of human cancers from nearly 8,000 tumor samples. Uhlén says his team was looking for “holistic changes across the genome caused by these mutations.”
They then mapped all the genes found in those cancer cells to find out how proteins made by these genes affect patient survival. Genes carry instructions for making proteins, and the level of gene expression increases or decreases the amount of protein that genes make. These resulting proteins can dramatically influence biological processes like cancer.
The researchers observed that the levels of proteins in different cancers varied widely, reinforcing the need for personalized cancer treatment based on the unique characteristics of a patient’s tumor, they say.
The researchers found that more than 2,000 genes had varying effects on a patient’s survival depending upon cancer type and where the tumor was located in the body. In some cases, genes that were more highly expressed were associated with better patient outcomes, and others predicted worse outlooks for patients. The results are detailed today in the journal Science.
Uhlén and his team identified another set of more than 2,000 genes that could potentially kill tumor growth but says affecting most of those targets with drugs would likely have severe side effects for patients. Of those, they predict 32 genes found in more than 80 percent of tumors, regardless of the cancer type, represent drug targets.
Previously, researchers have focused on using DNA sequencing to identify genetic mutations involved in cancer. To make this new atlas, scientists used RNA sequencing to understand how genes change when affected by cancer.
John Leite, vice president of oncology at the gene sequencing company Illumina, says lots of biological information will be needed to understand the underlying mechanisms that drive cancer formation and ultimately allow researchers and physicians to predict the best therapy options for patients. That’s where this new atlas could help.
Nicolas Robine, assistant director of computational biology at the New York Genome Center, says the atlas will be a useful resource for researchers, but said it can’t provide a definitive, automated answer to physicians wondering how a patient’s cancer will progress. “It’s not like you plug in your expression profile and it tells you whether you have a better or worse outcome.”
The atlas is part of a Swedish program started in 2003 with the aim of mapping all of the human proteins made by the body’s some 20,000 or more genes.