In a major breakthrough, scientists have found evidence that an important gene, which normally protects the body against cancer, can itself cause a variety of cancers depending on the mutation that damages it.
For the research, an international team, led by Ohio State University, has examined mutations in the PTEN gene.
People who inherit a mutated copy of this gene have Cowden syndrome, a condition that carries a high risk of cancer in a number of organs, including the breast, thyroid and ovary, according to the scientists.
In addition, PTEN is frequently mutated in normal body cells leading to prostate, lung and pancreatic cancers.
However, the scientists say that why people with Cowden syndrome develop different cancers, or cancers that are more severe in some than in others, is unknown, though the cause is often attributed to the natural genetic differences that exist between individuals.
This animal study, however, linked specific mutations in the gene to distinct kinds of cancer in organs targeted by the syndrome, the scientists say.
“We showed that the mutations themselves play a critical role in driving the cancers that occur in certain organs in people with Cowden syndrome. Together, our findings demonstrate that specific inherited PTEN mutations have strong influence in the variable predisposition to cancer of patients with Cowden syndrome,” said team leader Gustavo Leone.
According to the scientists, the findings suggest that testing for specific PTEN mutations might predict the kind and severity of cancer that will develop in people with syndrome.
Furthermore, because PTEN is the second most commonly mutated gene in human cancer overall, the same mutations might predict severity in sporadic tumors, as well.
For this study, the scientists developed three strains of genetically identical mice, each of which had one of three specific PTEN mutations found in people with Cowden syndrome.
This left each strain with a different version of the PTEN protein. The study showed that each version functioned in a different way, and each influenced cancer development to a different degree.
Mutation 1 disabled the protein altogether and often caused cancer in the animals, while mutation 2 produced a protein that was more active than the normal PTEN protein, and sometimes caused cancer.
Mutation 3 altered the protein in ways that should have made it more cancer-causing but also made it more fragile, so less of the protein was present to cause problems.
This mutation sometimes didn’t cause cancer at all.
Using a database of more than 400 patients with Cowden syndrome, the researchers found that patients with these same mutations have cancer in the corresponding organs as the mice, according to the findings published in the ‘Proceedings of the National Academy of Sciences’ journal.