From an analysis of more than 2,000 tumors spanning 12 types of human cancer, scientists have identified 27 new genes that could stop the disease in its tracks.
The discovery of these genes could open the door to much-needed personalized treatments for cancer, say the researchers.
First study author Jonas Demeulemeester, of the Francis Crick Institute in the United Kingdom, and colleagues recently reported their
Cancer arises when cells grow and divide uncontrollably, forming tumors.
Human cells normally contain two copies of tumor suppressor genes, which work to prevent tumor formation by slowing down cell division and growth. When these genes are deleted — through genetic mutations, for example — this gives rise to cancer development.
As a general rule, in order for tumors to form, both copies of the tumor suppressor genes must be malfunctioning in a cell. This is because a single functioning tumor suppressor gene can still produce the proteins needed to decelerate cell division and growth.
But the researchers note that identifying these double-gene abnormalities is challenging. One problem is that tumors often contain a mix of healthy and cancerous cells in varying proportions, making it difficult to determine whether one or two tumor suppressor genes are missing in cancer cells.
They have created a statistical model — which utilizes single nucleotide polymorphism analysis — that could help to overcome such problems. So far, it has helped them to identify an array of new tumor suppressor genes.
The researchers used their model to assess the number of tumor suppressor genes in the cells of 2,218 tumors across 12 types of cancer. These included breast, lung, colorectal, ovarian, and brain cancers.
The model not only enabled the team to calculate the relative proportions of healthy and cancerous cells in each tumor, making it easier to determine the presence of tumor suppressor genes in the cells, but it also revealed the distinct “DNA footprint” of tumor suppressor genes. This allowed them to distinguish these genes from non-harmful gene mutations.
As a result, the researchers identified a total of 96 gene deletions among the tumors. These included 43 tumor suppressor genes, of which 27 were previously unknown.
“Our study demonstrates,” explains senior study author Peter Van Loo, also of the Francis Crick Institute, “that rare tumor suppressor genes can be identified through large-scale analysis of the number of copies of genes in cancer samples.”
“Cancer genomics is a growing area of research, and the computational tools we use are a powerful way to find new genes involved in cancer,” he adds.
Cancer remains one of the biggest health burdens worldwide. There were around 14.1 million new cases of cancer diagnosed across the globe in 2012, with lung cancer, breast cancer, and colorectal cancer among the most common.
In the United States, more than
According to Demeulemeester and his colleagues, their findings may lead to personalized cancer therapies — that is, treatments that are tailored to individual patients based on the genetic makeup of their tumors.
“Using this powerful toolkit, we’ve uncovered rare tumor suppressor genes that when lost in mutated cells, cause cancer. This could pave the way for the development of personalized cancer treatments.”