Combined whole-exome tumor and blood sequencing identifies novel mutations in childhood cancer

In a new study published recently in JAMA Oncology, combined whole-exome tumor and blood sequencing identified mutations in pediatric cancer that could help to shed light on the cause of the disease, or may possibly have implications for clinical cancer care in 40% of patients.

The sequencing study, led by researchers from Baylor College of Medicine (BCM) and Texas Children’s Cancer Center (both TX, USA), revealed novel mutations in genes that had not previously been shown to be associated with the type of cancer diagnosed. Senior co-authors Sharon Plon (BCM) and Will Parsons (BCM and Texas Children’s Cancer Center) argue that this finding supports broad-based testing of both blood and tumor samples from children diagnosed with solid tumors.

A genetic mutation of possible clinical relevance was detected in the tumors of more than 25 % of the study patients, and Angushumoy Roy (BCM and Texas Children’s Hospital) commented that some of the mutations uncovered could potentially guide treatment selection in the event that tumors reoccurred. Germline mutations in adult and pediatric cancer susceptibility genes, which explained the cause of the cancer, were found in almost 10% of patients.

“Our findings were much broader than what we expected in both the tumor and the blood,” said Plon. “In a significant number of cases, results revealed mutations in genes that we would not even have thought of testing for, because they were not known to be associated with childhood cancer. These results suggest that using focused genetic testing could miss important findings.”

The research reported results from the first 150 newly diagnosed solid tumor patients who had been enrolled on the BASIC3 study at Texas Children’s Cancer Center – a project aiming to integrate blood and tumor whole-exome sequencing information from childhood cancer patients with solid tumors and brain tumors (obtained at the time of diagnosis) into their clinical care. The project is funded through a US$6.6 million grant from the National Human Genome Research Institute and the National Cancer Institute.

“An important aspect of this study is its focus on both what the tumor can tell us in terms of potential molecular targets for treatment but also what the blood samples reveal about the risk of hereditary cancer and other genetic diseases for the patient and their family,” stated Parsons.

“This is an important study and a powerful illustration of how genomic data can be effectively used by skilled physicians in a clinical context,” added Richard Gibbs, Director of the Human Genome Sequencing Center at BCM.

Source: Baylor College of Medicine press release