Kidney Week

Abstract: FR-PO908

Mutational Signature of Urothelial Carcinoma After Kidney Transplantation as Revealed by Whole-Exome Sequencing (WES)

Session Information

• Transplantation: Translational and Transplant Pathology
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 1802 Transplantation: Clinical

Authors

• Lim, Lee-Moay, Kaohsiung Medical University Hospital Division of Nephrology, Kaohsiung City, Taiwan

Lee-Moay Lim,

• Hwang, Daw-yang, Kaohsiung Medical University Hospital Division of Nephrology, Kaohsiung City, Taiwan

Daw-yang Hwang,

• Kuo, Hung-Tien, Kaohsiung Medical University Hospital Division of Nephrology, Kaohsiung City, Taiwan

Hung-Tien Kuo,

Background

Urothelial carcinoma (UC) has the characteristic of high degree molecular heterogeneity. In Taiwan, UC is the most common cancer after kidney transplantation(KT). Mutational profiles by WES could help in identifying not only UC-specific genes but also novel genes for disease specific therapeutic target and outcomes. We perform WES of UC developed after KT in an effort to discover the molecular genetics of UC.

Methods

Formalin-fixed paraffin-embedded archival samples of UC from 6 kidney transplant patients in our center were obtained. Patients with UC diagnosed before the transplant surgery were excluded. All patients were sporadic, without any family history of UC. For control group, we selected 5 hemodialysis patients with UC diagnosed after the commencement of dialysis treatment. DNA was extracted for WES analysis.

Results

Missense mutations were the most common type of somatic mutation (Figure 1a, 2). The A:T→T:A transition was the most significant nucleotide changes (Figure 1b). Our WES data was matched with the Cosmic, Intogen, and TCGA database for onco-driver genes. We newly identified five genes, including GNAQ, MLLT10, SEPT6, SLC34A2, NTRK3, which comprised of 25% of mutations specifically in our patients (Figure 2).

Conclusion

The finding of A:T→T:A transition as the most significant nucleotide changes was different from TCGA cohort, as about 51% of their mutation resulted in TpC>T or G. Our results suggest that the genetic mutation in our cohort might be associated with aristolochic acid (AA) exposure, which is the one of the risk factor for renal failure and UC development. This preliminary data provides clues for understanding the mutational landscape of UC developed after KT.