GENOME sequencing from 234 members of 36 families with two or more first-degree relatives with a diagnosis of Hodgkin lymphoma, with at least one diagnosis occurring before the age of 21 years, has revealed 44 genetic variants associated with increased risk.
The collaborative study co-lead by Jamie Flerlage, Department of Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA, and Jason Myers, Center for Applied Bioinformatics, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA, utilised a combination of family pedigrees, genome sequencing, and bioinformatics to help determine whether there is any heritability in Hodgkin lymphoma. Myers stated that the strategy they used allowed the team to “process data from these families in a meaningful way”, with Flerlage adding that this study was important to “help us better counsel people about their chances of passing on genetic risk to their offspring, as well as help us identify novel targets that might potentially be used to create new treatments.”
The research team developed family pedigrees from families treated at St. Jude Children’s Research Hospital and families included in the National Cancer Institute’s familial lifetime cohort study, to track Hodgkin lymphoma diagnoses within families and performed whole genome sequencing to enable a deeper evaluation for any potential gene variants that were associated with increased risk for developing Hodgkin lymphoma, including epigenetic and non-coding genetic variants.
Sequencing identified multiple novel gene variants, including EEF2KMT, GATA3, IRF7, PAX5, and POLR1E. These variants were then tracked through family pedigrees using a bioinformatics pipeline developed at St. Jude Children’s Research Hospital. Essentially, algorithms were able to identify which variants occurred in participants and then trace these variants through the family pedigree to determine which variants were associated with Hodgkin lymphoma within that family.
The findings from this research will help clinicians provide families with insightful information and improve understanding. Furthermore, Myers commented on how the bioinformatics pipeline has applications beyond Hodgkin lymphoma, stating that “the pipeline can be used for any other disease where families are involved”, highlighting future hope for genetic counselling in other inherited diseases.