Washington: Scientists claim to have uncovered a critical genetic mutation in some patients with myelodysplastic syndromes -- a group of blood cancers that can progress to a fatal form of leukaemia.
A team at Washington University School of Medicine has also found evidence that patients with the mutation are more likely to develop acute leukaemia.
The research in the `Nature Genetics` journal, raises the prospect that a genetic test could one day more accurately diagnose the disorder and predict the course of the disease, say the scientists.
In fact, they discovered the mutation in a gene known as U2AF1 when they sequenced the entire genome of a 65-year-old man with myelodysplastic syndrome that had progressed to leukaemia and compared it with the genome of his tumour cells.
They also found the genetic error in other patients with myelodysplastic syndromes, an indication of the mutation`s significance.
"The mutation in this gene was not on anyone`s radar screen. In many cases, the diagnosis of myelodysplastic syndromes is unclear because there isn`t a straightforward diagnostic test.
"By understanding at the genetic level what is contributing to this disease, we hope to eventually improve the diagnosis and treatment of this disorder," lead scientist Matthew Walter said.
Myelodysplastic syndromes are a difficult-to-treat family of blood cancers that occur when blood cells in the bone marrow don`t mature properly.
In about 30 percent of cases, the disorder progresses to a form of acute myeloid leukaemia that usually is fatal because chemotherapy drugs are not effective in these patients.
Doctors currently assess the likelihood that a patient with myelodysplastic syndrome will develop leukaemia by looking at the chromosomes in the tumour cells to determine the extent to which they have broken apart and rearranged themselves, an indicator of the severity of the disease.
"There are chromosomal patterns that indicate high risk and low risk, but the current methods to determine prognosis aren`t perfect," said team member Timothy Graubert.
After identifying the U2AF1 mutation in three patients through whole-genome sequencing, the researchers scoured the gene for the mutation in another 150 patients with myelodysplastic syndromes.
They identified the mutation in 13, or nearly nine per cent. The mutations were acquired during development of myelodysplastic syndromes because they were not present in normal cells obtained from each patient.
Patients were almost three times as likely to develop leukaemia if they had a mutation in the U2AF1 gene. The disorder progressed to leukaemia in 15.2 percent of patients with the mutation, compared with 5.8 percent of those without the genetic error.
The most common mutation results in a single letter change in the DNA at a precise location in the U2AF1 gene.