Novel Cancer Genes Discovered Via New Statistical Model - NFCR


Novel Cancer Genes Discovered Via New Statistical Model

LONDON — A new statistical model developed by scientists at the Francis Crick Institute
revealed 27 novel genes thought to prevent cancer from forming, in an analysis of over 2000
tumors across 12 human cancer types. The findings could help create new cancer treatments that
target these genes, and open up other avenues of cancer research. Novel genes are generally
duplicated genes that develop new (thus, “novel”) functions.

“Using this powerful toolkit, we’ve uncovered rare tumor suppressor genes that when lost in
mutated cells, cause cancer” says researcher Jonas Demeulemeester. “This could pave the way
for the development of personalized cancer treatments.”

Mutation is a necessary component of evolution, but not all mutations are benevolent. To combat
virulent mutations that can lead to tumors, each individual human cell has two copies of tumor
suppressor genes to prevent it from turning cancerous. If one of these genes is lost, the other can
pick up the slack, but if both genes are lost, tumor formation is free to occur and the body may not
see it as harmful.

The identified double gene copy deletions can provide clues for tumor suppressor genes in
cancer. However, cancer samples normally contain both healthy cells and cancerous cells in
unknown proportions, making it difficult to work out if just a single copy or both copies of the gene
have been lost in the cancer cells.

In addition, cancer is not a single, straightforward mutation; it can be difficult to distinguish
between harmful deletions of tumor suppressor genes and non-harmful deletions of other genes
at fragile sites along the genome. Just as not all mutations are benevolent, not all are virulent, or
even effectual. Scientists can investigate the new candidate tumor suppressor genes identified in
this study to understand their mechanism of action, and try to find drug targets.

The Frick team developed computational tools to analyze 2,218 tumors from 12 cancer types
including breast, lung, and bowel cancers. By determining the relative proportions of cancerous
and healthy cells in each sample, they could work out the number of copies of each gene in the
cancer cells. This analysis revealed 96 regions of the human genome that are frequently lost
during tumor development.

The analysis also revealed that harmful tumor suppressor gene deletions have a different “DNA
footprint” to non-harmful deletions. This enabled the researchers to categorize deletions,
revealing 16 previously known tumor suppressor genes, and 27 new ones. Some of these had
previously been suspected to contribute to cancer development, while others were completely

“Cancer genomics is a growing area of research,” says Peter Van Loo, group leader at the
Francis Crick Institute, “and the computational tools we use are a powerful way to find new genes
involved in cancer.”

The research, published in Nature Communications, was led by scientists at the Francis Crick
Institute and the University of Leuven, in collaboration with the University of Chicago and the
University of Oslo.