A family case with germline TSC1 and mtDNA mutations developing bilateral eosinophilic chromophobe renal cell carcinomas without other typical phenotype of tuberous sclerosis

We examined the genetic alterations in a mother and son with multiple eosinophilic chromophobe renal cell carcinomas (chRCCs) showing no other features.

Germline DNA and bilateral renal cell carcinoma DNA were genetically analysed by whole-exome sequencing. Candidate gene alterations in the first patient's germline were investigated in her child's germline and the chRCCs.

We detected several germline gene alterations in the mother. Among the identified alterations, TSC1 and mitochondrial DNA mutations were also confirmed in her son. Regarding somatic alterations in bilateral chRCCs, no common candidate gene alteration was found.

To the best of our knowledge, this is the first report of whole-exome sequencing revealing bilateral eosinophilic chRCCs associated with tuberous sclerosis complex in a family case without classical phenotype. These results suggest that germline TSC1 and mitochondrial DNA gene mutations may be involved in the development of chRCCs in some cases.

Journal of clinical pathology. 2018 Jun 30 [Epub ahead of print]

Hiromasa Sakamoto, Toshinari Yamasaki, Takayuki Sumiyoshi, Noriaki Utsunomiya, Masashi Takeda, Tomomi Kamba, Eijiro Nakamura, Osamu Ogawa

Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan., Department of Urology, Kumamoto University Graduate School of Medicine, Kumamoto, Japan., Department of Laboratory for Malignancy Control Research/Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.