The discovery of the ETV6 mutation may help doctors to increase monitoring and in the future prevent the disease.
The study, conducted by the University of Colorado Cancer Centre, pinpoints a newly discovered heritable genetic cause of acute lymphoblastic leukemia (ALL), specifically a mutation of the gene ETV6.
The mutation of the BRCA gene marks people, most famously Angelina Jolie, with an increased risk of developing breast and ovarian cancers. The identification of the mutation of the ETV6 gene may allow doctors to predict the development of ALL in people, in the same way.
Insight of the ETV6 mutation may help doctors to increase monitoring and to develop strategies to prevent the disease. There are around 30,000 cases of ALL diagnosed in the US each year, with a majority of cases in children aged 2-5.
"These people are born with a broken gene and it sets them up for leukemia," says Dr. Chris Porter, investigator at the CU Cancer Center and associate professor in the Department of Pediatrics at the CU School of Medicine.
Porter indicates that the finding began with a family that had an abnormally high rate of ALL. They all had similar traits of big red blood cells, low platelet counts and a tendency to bleed.
The fact that the family had abnormal blood dynamics and predisposition implied a common genetic denominator. The scientist's task was to investigate exactly what, in the family's genes, produced the blood problems.
The investigators performed "whole exome sequencing" of the family members that were predisposed to ALL to take a snapshot of each protein-producing gene in their chromosomes.
ETV6 mutation and ALL risk runs in families
The data from the sequencing was analyzed by bioinformaticist Ken Jones, PhD; to compare the high-risk genomes predisposed to develop ALL with normal-risk healthy genomes. The key difference between the two was mutation of the gene ETV6.
The ETV6 gene provides instructions for producing a protein that functions as a transcription factor, which means that it attaches (binds) to specific regions of DNA and controls the activity of certain genes. ETV6 is involved in the development of blood cells.
In previous studies, "somatic" mutations of the ETV6 gene (mutations in the genome that are not present at birth but later develop) have been associated with the development of blood cancers. Somatic mutation of the ETV6 gene requires other "helper" mutations to cause ALL.
However, this study, published in the journal Nature Genetics, is one of two new reports to demonstrate that "germline" mutations of ETV6 (an abnormality that is heritable and present in the genome at birth) can also cause cancers. This highlights that the mutation and risk can run in families.
Dissimilar to somatic mutation of the ETV6 gene, a germline mutation places a patient one step closer to the development of leukemia from birth.
Porter and colleagues aim to reveal the prevalence of the ETV6 mutation in future studies.
"It's not common in a general population," Porter comments, "but we think it might be much more common in people who develop ALL."
Porter's comment means that of all people that develop ALL, heritable mutation of the gene ETV6 may be a cause in some cases.
"The paper highlights this gene in the development of leukemia. By studying this mutation, we should be able to gather a better understanding of how leukemia develops."
Medical News Today recently reported that scientists have discovered how to reprogram dangerous leukemia cells to mature into harmless immune cells.