Tumor Resident, B-Cell Receptor Chemical Characteristics Associated with Better Overall Survival for Neuroblastoma

Pediatric neuroblastoma (NBL) is one of the most common pediatric cancers, and it can often be aggressive. Genetic and demographic factors can correlate with the severity of NBL, but the variations in the B-cell receptors (BCRs) or immunoglobulin proteins present in the NBL tumors, and their relationships to survival, are not well understood. BCRs contain variations in their complementary determining region-3 (CDR3s) amino acid sequences, due to variable recombinations of the V- and J-gene segments. Accordingly, these variations in CDR3s may represent different antigen interactions and thereby different survival probabilities. Thus, we mined the TARGET project, NBL tumor RNAseq files for BCR recombination reads. Evaluations of the physicochemical properties of IGK, IGL, and IGH CDR3s from these tumors pointed to properties of IGK and IGL in particular as associated with survival distinctions, based on several independent bioinformatics approaches, including a novel homology grouping approach facilitated by a recently developed web tool, adaptivematch.com. In conclusion, tumor resident BCR chemical features are likely useful for better risk stratification and for guiding therapy, and the availability of a user-friendly web tool will likely facilitate using BCR chemical features to meet those goals.