Abstract
BACKGROUND
The Molecular Characterization Initiative (MCI) sponsored by the National Cancer Institute (NCI) as part of the Childhood Cancer Data Initiative provides free clinical molecular testing with return of results to treating institutions.
METHODS
The MCI was activated as an optional sub-study of the COG Project:EveryChild registry, eligibility screening, biology and outcome study. Eligibility for subjects with central nervous system (CNS) tumors included newly diagnosed benign and malignant tumors in subjects < 25 years. Clinical testing included exome sequencing of paired tumor/normal; DNA methylation array for CNS tumor classification; and targeted RNA sequencing for fusion detection. Required specimens were tumor (snap frozen, FFPE block or slides) and whole blood. Quality control confirming presence and percentage of tumor was confirmed by central pathologist. Minimum nucleic acid yield included 300ng DNA (frozen, 700ng from fixed tissue) and 500ng RNA.
RESULTS
In the first 10 months since activation 3/21/2022, 867 CNS subjects from 149 COG institutions have enrolled in the MCI, of which 675 (78% of enrolled) have submitted both required tumor and blood specimens. Adequate nucleic acids were extracted from 592 specimens (88% of submitted). For subjects with adequate nucleic acids, DNA exome and methylation classification results were returned for 99%; RNA fusion analysis was returned for 93%. Median time to return of results was 19 days from receipt of tumor specimens. Only 16% of CNS subjects were also participating in screening for COG therapeutic studies, including medulloblastoma (7%), low-grade glioma (6%) and high-grade glioma (4%). Genomic and annotated clinical data are available within the NIH-sponsored repository, dbGAP, through controlled access request by academic investigators.
CONCLUSIONS
The MCI represents an unprecedented resource of genomic and clinical data that is readily available to improve clinical diagnosis and support pediatric brain tumor research.