Study Traces Bladder Cancer Risk Contributors in Organ Transplant Recipients

For a paper appearing in eLife, researchers at the National Cancer Institute, Leidos Biomedical Research, and elsewhere look at potential contributors to bladder cancer risk in immunosuppressed solid organ transplant recipients, including the presence of potentially oncogenic DNA viruses such as the BK polyomavirus (BKPyV), which was previously found in up to one-quarter of transplant recipients' tumors. Using a combination of whole-genome sequencing and RNA sequencing, the team found recurrent somatic mutations, mutation signatures, and viral sequences in archived tumor samples from 43 solid organ transplant recipients who went on to develop bladder cancer. Along with mutation signatures linked to APOBEC3 mutagenesis and other mutations or environmental exposures, the authors tracked down BKPyV sequences in nine tumor samples, while flagging sequences from other viruses in more than a dozen additional samples. From these and other results, they suggest that "a subset of tumors of solid organ transplant recipients develop through distinct mutagenic processes compared to the general population," and argue that their results "indicate multiple distinct mechanisms of carcinogenesis in bladder cancers of solid organ transplant recipients that may have implications for prevention, treatment, and outcome."