The study was done by sequencing breast tumor samples from 560 patients, 556 were women, and four were men. This is the largest ever sequencing effort for breast cancer mutations.
In the resulting DNA sequences, the researchers searched for variations in genes that cause healthy cells to turn cancerous. "All cancers are due to mutations that occur in all of us in the DNA of our cells during the course of our lifetimes," said Mike Stratton, director of the Wellcome Trust Sanger Institute. "Finding these mutations is crucial to understanding the causes of cancer and to developing improved therapies."
The team identified 93 genes, which, when mutated, lead to breast tumors. While this list contains some already known suspects, such as BRCA1 and BRCA2, five genes on the list are new. Furthermore, they identified 12 new mutational signatures arising in patient tumors. Even in BRCA1/2, the team found highly specific mutational signatures that unique to some patients and not seen in others.
"There are about 20,000 genes in the human genome. It turns out, now we have this complete view of breast cancer - there are 93 of those [genes] that if mutated will convert a normal breast cell into a breast cancer cell. That is an important piece of information,” said Professor Sir Mike Stratton, director of the Sanger Institute in Cambridge, and senior study author.
Barring new and rare mutations that arise spontaneously, the team boldly claimed that their list is definitive and conclusive. Whether the gene list is truly complete will only be revealed with extended sequencing on more samples. In the mean time, the team plans to give the list of 93 genes to “the universities, the pharmaceuticals, the biotech companies to start developing new drugs because those mutated genes and their proteins are targets for new therapeutics,” said Stratton.
"This study both gave us the first large-scale view of the rest of the genome, uncovering some new reasons why breast cancer arises, and gave us an unexpected way to characterize the types of mutations that happen in certain breast cancers," said Ewan Birney, study co-author.
The list of genes and their associated mutations could be used to predict breast cancer risks in patients, especially for the hereditary types. In addition, knowing the specific mutations in a patient could allow doctors to custom-tailor treatments for every patient. "In the future, we'd like to be able to profile individual cancer genomes so that we can identify the treatment most likely to be successful for a woman or man diagnosed with breast cancer. It is a step closer to personalized healthcare for cancer," said Serena Nik-Zainal, first study author from the Wellcome Trust Sanger Institute in the United Kingdom.
Additional sources: Wellcome Trust Sanger Institute, BBC, MNT