Albuquerque, NM – UNM Cancer Center researchers, including the Center’s director and CEO, Cheryl Willman, M.D., have undertaken the largest pediatric cancer genome sequencing effort reported to date.
As described in a recent paper in the scientific journalBlood( prepublished online June 16 ), the researchers, part of the multi-institutional Children’s Oncology Group, sequenced 120 genes in 187 samples of high-risk acute lymphoblastic leukemias from children with the disease. The genes chosen for sequencing were selected strategically to include genes known to have altered expression in acute lymphoblastic leukemia ( ALL ) and genes commonly mutated in other cancers.
And indeed, researchers found a high frequency of recurrent mutations in four key signaling pathways responsible for everything from cell growth, differentiation and survival to tumor suppression. Moreover, they discovered that these recurrent mutations vary markedly across different genetic subtypes of ALL ( that is, distinct patterns of genes associated with the disease ).
The team’s findings both extend the range of genes known to mutate regularly in high-relapse forms of pediatric ALL and highlight important new therapeutic targets for certain groups of young patients with the disease.
ALL is the most common childhood cancer. Approximately 5,000 children in the U.S. are diagnosed with the disease each year, including about 45 New Mexican kids. Once a death sentence, pediatric ALL is now considered highly treatable, with five-year survival rates nearing 85 percent. Still, up to 20 percent of children treated for ALL will relapse, and these children are much less likely to ultimately survive the disease: post-relapse, five-year survival rates dip to just 30 percent. Better understanding what drives treatment resistance and promotes relapse is thus an urgent priority in ALL research.
The UNM Cancer Center’s Cheryl Willman is one of three lead investigators on the present study and a co-author of the latestBloodpaper. She and Children’s Oncology Group colleagues from St. Jude Children’s Research Hospital and the University of Colorado are recipients of the National Cancer Institute’s TARGET funding. TARGET, short for Therapeutically Applicable Research to Generate Effective Treatments, seeks to identify valid therapeutic targets in childhood cancers so that new, more effective treatments can be rapidly developed.
Willman and colleagues, part of a TARGET initiative focused on ALL, are using genomic approaches and high-throughput gene sequencing to identify new targets for treating pediatric ALL. It is out of this research that previous findings related to Native American genetic ancestry and ALL relapse risk emerged. In the current study, the research team is specifically investigating ALL cases that relapse within 36 months of diagnosis in an effort to better understand the genomic changes associated with treatment failure.