Between one and 10 driver mutations are required for cancer to develop, according to a team from the Wellcome Trust Sanger Institute. The researchers studied more than 7,500 tumors across 29 different cancers.
This is the first time that researchers have “provided unbiased estimates of the number of mutations” that are needed for cancer to emerge. Their findings — which have been published in the journal Cell — also reveal that the number of mutations required to drive cancer significantly varies depending on the type of cancer.
The study was conducted by lead author Dr. Peter Campbell, first author Dr. Iñigo Martincorena, and co-author Prof. Michael Stratton, all of whom are from the Wellcome Trust Sanger Institute in the United Kingdom.
“We have addressed a long-standing question in cancer research that has been debated since the 1950s: how many mutations are needed for a normal cell to turn into a cancer cell?” says Dr. Campbell.
“The answer is,” he adds, “a small handful. For example, about four mutations per patient on average drive liver cancers, whereas colorectal cancers typically require 10 or so driver mutations.”
The Wellcome Trust Sanger Institute and collaborators identified a strategy to distinguish the genes that are involved in cancer evolution and the number of mutations in those genes that play a role in causing cancer. This approach could be used in the future to help clinics identify the few mutations, among thousands, that are driving cancer in an individual patient.
Charles Darwin described, more than 150 years ago, how various species evolve through natural selection. Cancer similarly occurs by the natural selection process, acting on the mutations that develop in our bodies’ cells over time.
The researchers applied an evolutionary perspective to quantify the process of natural selection in their analysis of 7,664 tumors across 29 cancer types. The team cataloged the primary cancer genes involved in 29 types of cancer.
Furthermore, they discovered new genes associated with cancer and attempted to clarify the completeness of the current lists of cancer genes.
“In the study,” says Dr. Martincorena, “we revealed that around half of these key mutations driving cancer occur in genes that are not yet identified as cancer genes.”
“There is already much insight into the most important genes involved in cancer, but there are many more genes yet to be discovered. We will need to bring together even larger numbers of cancers studied by DNA sequencing, into the tens of thousands, to find these elusive genes,” he adds.
Eventually, the techniques utilized in this study could be used to improve personalized cancer care. Similar methods could be used in a clinical setting to set apart the particular mutations, of the thousands that are apparent in each tumor, responsible for a patient’s cancer.
“We now know of hundreds of genes, that when mutated, drive cancer. This research shows that across cancer types a relatively consistent small number of mutated genes is required to convert a single normal cell into a cancer cell, but that the specific genes chosen differ according to cancer type.”
Prof. Michael Stratton
The study highlights that many of the driver genes have not yet been identified, notes Prof. Stratton, and they will be the target for additional research.
“This increasingly precise understanding of the underlying changes that result in cancer,” Prof. Stratton concludes, “provides the foundation for the discovery and use of targeted therapies that treat the disease.”