Whole exome sequencing identified mutations of forkhead box I 1 (FOXI1), keratin 6 C (KRT6C) and gap junction protein delta 2 (GJD2) in a low-grade oncocytic tumor of the kidney: a case report.

Background: Low-grade oncocytic tumor (LOT) of the kidney is an emerging entity among renal oncocytic tumors. While the histological features of LOT of the kidney are similar to those of renal oncocytoma, LOT immunohistochemically expresses keratin 7 (KRT7) but not KIT while renal oncocytoma expresses KIT. Molecular analyses of LOTs of the kidney using next generation sequencing revealed those tumors harbor mutations of mTOR-related genes.

Case Presentation: An 80-year-old Japanese man with a history of clear cell renal cell carcinoma and prostatic cancer underwent resection of the tumor of the right kidney, 10 mm in diameter, which was monitored for six years. The tumor was histologically composed of oncocytic cells that expressed KRT7, vimentin, SDHA, SDHB and fumarate hydratase, but not KIT, GATA3 and alpha-methylacyl-CoA racemase. We diagnosed the tumor as LOT of the kidney. Whole-exome sequencing of the LOT revealed single nucleotide variants in the DNA-binding region of forkhead box I1 (FOXI1), the coil 1B domain of keratin 6 C (KRT6C) and the intracytoplasmic region of gap junction delta 2 (GJD2), which encodes connexin 36. However, there was no mutations in mTOR-related genes. No copy number alterations were detected in the tumor.

Conclusions: We report three mutations in genes that have not been previously reported in LOT of the kidney. The genes are not related to the mTOR pathway. Therefore, LOT of the kidney might occur through several mechanisms and/or include several types of renal oncocytic tumors.