Mutational Profiles of Urothelial Cancer Samples after Kidney Transplantation - Expert Commentary

There is a well-documented increase in the risk of cancer development after a kidney transplant. For example, Lim et al. recently published a whole-exome sequencing analysis of somatic mutations in patients who underwent kidney transplants and subsequently developed urothelial carcinoma.

The study cohort consisted of 12 urothelial tumor samples, with 7 from urothelial cancer patients who received a kidney transplant and five from urothelial cancer patients who were on hemodialysis (controls). All patients were female, and 10 out of 12 had high-grade tumors. The analysis revealed 18,733 and 11,093 variants in the kidney transplant and hemodialysis groups, respectively. In addition, the authors identified 14 novel mutations of CARD11, FNBP1, GNAQ, HOXD13, IKZF1, MAX, MLLT10, NTRK3, SEPTIN6, SEPTIN9, SH3GL1, SLC34A2, TAL1, and TRAF7. Interestingly, the contribution of the COSMIC Single-base substitutions (SBS) signature 22, attributed to Aristolochic acid exposure and characterized by higher T>A substitutions, was higher in all patients in this cohort. This is in line with previous studies that showed a link between this substance, found in herbal therapies common in Taiwan, and tumorigenic changes contributing to urothelial cancer.

The findings in this study provide insight into some aspects of tumor mutagenic processes following kidney transplantation. However, further studies on the roles of the identified genes will also be needed for functional validation and a better understanding of underlying mechanisms contributing to tumorigenesis in the context of transplant. Furthermore, the role of viral genomic integration in urothelial tumorigenesis due to immunosuppression in solid organ transplant patients is currently not well understood.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine

References:

  1. Lim, LM., Chung, WY., Hwang, DY. et al. Whole-exome sequencing identified mutational profiles of urothelial carcinoma post kidney transplantation. J Transl Med 20, 324 (2022). https://doi.org/10.1186/s12967-022-03522-4

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