A genetic defect in sex cells may predispose to childhood leukemia

December 17, 2012

Researchers at the Sainte-Justine University Hospital Center and the University of Montreal have found a possible heredity mechanism that predisposes children to acute lymphoblastic leukemia (ALL), the most common type of blood cancer in children. According to their findings published in Genome Research, the presence of a genetic defect in the egg or sperm from which children having ALL arise may be a prerequisite for the disease to develop. A significant number of children with ALL are thought to inherit a rare PRDM9 gene variant responsible for the abnormal sex cells–a gene variant that puts their own children at risk of having ALL-predisposed offspring.

"Our findings indicate ALL susceptibility to be partially hereditary. However, it is not classic heredity in the sense that the abnormal genetic variant does not need to be passed from parent to child for offspring to have the disease," explains Julie Hussin, a doctoral student in Genomics under the direction of Dr. Philip Awadalla, a genetics researcher.

"Instead, the genetic defect in the egg or sperm from which the children developed is thought to predispose them to leukemia," continues Julie Hussin. "However, only the children who inherit the genetic variant run the risk of transmitting ALL predispositions to their offspring." According to the study, more than three fourth of families with affected children have an atypical form of the PRDM9 gene, but only half the patients inherited this genetic variant. The defect is expressed by chromosome recombinations at unusual points during gamete formation (eggs in girls, sperm in boys).

While an abnormal gamete may lead to ALL development, this condition alone is not enough. "Triggering the process of cancer inevitably requires a second hit, such as other mutations or environmental factors," explains Julie Hussin.

Until now, few pediatric have analyzed data from parents, as scientists generally focus on studying children, their tumors or their environment, especially during pregnancy. "Parents have to be included in these studies. Our findings demonstrate the importance of including parents' genetic information for the understanding of childhood leukemia, as well as other early childhood diseases," added Dr. Philip Awadalla, the lead principal investigator on the study.

The findings were replicated in a cohort of American children with ALL through a collaboration of the Sainte-Justine University Hospital Center in Montreal, Canada, and St. Jude Children's Research Hospital in Memphis, USA.

Explore further: Genetic make-up of children explains how they fight malaria infection

More information: Rare allelic forms of PRDM9 associated with childhood leukemogenesis in Genome Research, December 5, 2012. genome.cshlp.org/content/early/2012/12/05/gr.144188.112.abstract

Related Stories

Gene responsible for relapses in young leukemia patients

October 26, 2011

One of the causes of resistance to cancer treatment in children is now beginning to be elucidated. Acute lymphoblastic leukemia patients with a particular form of the ATF5 gene are at higher risk of having a relapse when ...

Recommended for you

Epigenetic factors linked to obesity-related disease

January 17, 2017

Obesity has been linked to "letter" changes at many different sites in the genome, yet these differences do not fully explain the variation in people's body mass index (BMI) or why some overweight people develop health complications ...

Are you ready to explore baby's genome?

January 17, 2017

When you have a baby, a nurse or a phlebotomist performs a heel stick to take a few drops of blood from your infant and sends it off to a state lab for a battery of tests. Most of the time, you never hear about the results ...

Study applies game theory to genomic privacy

January 17, 2017

It comes down to privacy—biomedical research can't proceed without human genomic data sharing, and genomic data sharing can't proceed without some reasonable level of assurance that de-identified data from patients and ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.