A multicenter team of childhood cancer researchers has discovered two genetic variations linked to an increased risk for acute lymphoblastic leukemia, or ALL, the most common childhood cancer in the United States.
Because these genetic glitches point to a specific subtype of the disease, identifying them in children who already have leukemia could improve treatment, says University of Florida researcher Meenakshi Devidas, Ph.D., a co-author on the study published online Sunday in Nature Genetics. Children with this specific subtype of ALL, known as B-hyperdiploid, tend to respond well to chemotherapy.
“The findings indicated inherited genetic variants contribute to the risk of a child getting ALL and likely contribute to a specific subtype of ALL,” said Devidas, a research associate professor in the department of epidemiology and health policy research in the UF College of Medicine and co-director of the Children’s Oncology Group Statistics and Data Center at UF. “So far, we have known that patients with this subtype respond well to chemotherapy, but we had no idea why that was.”
Led by St. Jude Children’s Research Hospital scientist Mary Relling, Pharm.D., the researchers conducted the first genomewide association study to check for genetic variations linked to the common cancer.
“This work indicates that as we approach full sequencing of cancer genomes, we should account for the fact that a gene can be made ‘abnormal’ via both inherited and acquired defects, and so we should not discount subtle inherited genomic variation as contributing to cancer risk,” said Relling, chair of the St. Jude Children’s Research Hospital department of pharmaceutical sciences and the paper’s senior author. “With projects such as these, our collaboration with members of the Children’s Oncology Group, which provided additional cases for genetic analysis, helped strengthen our findings.”
To identify these genetic variations, the researchers analyzed the genetic makeup of about 400 children with acute lymphoblastic leukemia. After numerous tests, the researchers discovered two variations in tiny strands of DNA — known as single-nucleotide polymorphisms — that pointed to an increased risk for the disease and were also linked to the B-hyperdiploid subtype.
“If a patient has B-hyperdiploid ALL and has the genetic variation then we can at least project that this patient will do well,” Devidas said. “Not that all patients do well, but if they have it the chances are higher.”
Nearly one-quarter of children with cancer have ALL, National Cancer Institute statistics show. The disease occurs when abnormal white blood cells flood a person’s bone marrow, killing the normal white blood cells needed to fight infections. Because of scientific research, the survival rate for this form of leukemia is around 85 percent, up from 5 percent in the 1960s, according to the National Cancer Institute.
The researchers who collaborated on the study are members of the Children’s Oncology Group, the only National Institutes of Health/National Cancer Institute pediatric cancer cooperative group. The group performs clinical trials, collects specimens and performs statistical analysis related to pediatric cancers. UF is one of three institutions with a branch of the COG Statistics and Data Center, where study design, data collection and statistical analysis for COG research occurs.