Researchers say they have discovered an important molecular link between Fanconi anemia (FA) and PTEN, a gene associated with uterine, prostate, and brain cancer.
They say this discovery enhances our understanding of the molecular basis of Fanconi anemia and could lead to improved treatment outcomes for both Fanconi anemia and cancer patients.
The researchers detailed their discovery in Scientific Reports.
They explained that Fanconi anemia proteins function primarily in DNA interstrand crosslink (ICL) repair, and they wanted to determine the role of the PTEN phosphatase in this process.
“The PTEN gene codes for a phosphatase—an enzyme that removes phosphate groups from proteins,” said study author Niall Howlett, PhD, of the University of Rhode Island in Kingston, Rhode Island.
“Many Fanconi anemia proteins have phosphate groups attached to them when they become activated. However, how these phosphate groups are removed is poorly understood.”
With this in mind, the researchers performed an experiment to determine if Fanconi anemia and PTEN are biochemically linked.
The team knew that cells from Fanconi anemia patients are sensitive to ICL-inducing agents, so they set out to determine if PTEN-deficient cells are sensitive to these agents as well.
“By testing if cells with mutations in the PTEN gene were also sensitive to [ICL-inducing] agents, we discovered that Fanconi anemia patient cells and PTEN-deficient cells were practically indistinguishable in terms of sensitivity to these drugs,” Dr Howlett said.
“This strongly suggested that the Fanconi anemia proteins and PTEN might work together to repair the DNA damage caused by [ICL-inducing] agents.”
Using epistasis analysis, Dr Howlett and his colleagues found that Fanconi anemia proteins and PTEN do indeed function together in ICL repair.
“Before this work, Fanconi anemia and PTEN weren’t even on the same radar,” Dr Howlett said. “This is really important to understanding how this disease arises and what its molecular underpinnings are. The more we can find out about its molecular basis, the more likely we are to come up with strategies to treat the disease.”
Dr Howlett and his colleagues believe their research is equally important to cancer patients. Since this study showed that cells missing PTEN are highly sensitive to ICL-inducing agents, the team believes it should be possible to predict whether a particular cancer patient will respond to this class of drugs by conducting a simple DNA test.
“We can now predict that if a patient has cancer associated with mutations in PTEN, then it is likely that the cancer will be sensitive to [ICL-inducing] agents,” Dr Howlett said. “This could lead to improved outcomes for patients with certain types of PTEN mutations.”
