Scientists have long wondered how many genetic mutations have to occur within a cell for it to become cancerous. Now researchers have attempted to answer that question, assessing over 7,500 tumors taken from 29 different kinds of cancer. They found a wide range; anywhere from one to ten mutations can drive a cell toward cancer. Reporting in the journal Cell, it seems that different kinds of cancer have different mutational characteristics.
"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? The answer is: a small handful,” explained the lead author of the work, Dr Peter Campbell, of the Wellcome Trust Sanger Institute. “For example, about 4 mutations per patient on average drive liver cancers, whereas colorectal cancers typically require 10 or so driver mutations."
Mutation in our genetic material is a natural part of biology, and it can propel species forward through evolution in positive ways. Natural selection can weed out the good and bad mutations. However, genetic mutations can also lead to cancer. For this work, the researchers wanted to quantify the mutations that were accumulating in 7,664 tumors.
Scientists from the Wellcome Trust Sanger Institute and collaborators created a technique that identifies genes that influence cancer evolution, and how mutations that build up in those genes can propel cancer. This work might one day be useful in the clinic so that the mutations driving cancer in individual patients can be pinpointed. The methods utilized in this work may also help personalize cancer therapy.
Interestingly, this work has also shown that mutations are often well-tolerated by the cells in our bodies. Mutations that people inherit from parents are usually detrimental and tend to be lost from the human genome as time goes on. However, when a cell in the body develops cancer, the associated mutations tend to persist without having a negative impact on cell survival.
Additionally, new cancer genes have been identified. The investigators found the main genes responsible for 29 different cancers. Several new ones were identified, showing how complete cancer gene lists are.
"In the study, we revealed that around half of these key mutations driving cancer occur in genes that are not yet identified as cancer genes,” said first author Dr. Inigo Martincorena of the Wellcome Trust Sanger Institute. “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."
Professor Sir Mike Stratton, an author of the study and director of the Wellcome Trust Sanger Institute, said: "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 such 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. The study also shows that we have not yet identified many these driver genes and they will be the target for further searching in the future. This increasingly precise understanding of the underlying changes that result in cancer provides the foundation for the discovery and use of targeted therapies that treat the disease."
Learn more about DNA mutations and cancer from the video.