Somatic mitochondrial DNA mutations in human chromophobe renal cell carcinomas.

We sequenced the entire mitochondrial genome in 8 chromophobe renal cell carcinomas (RCCs) and corresponding normal kidneys. Our study disclosed 68 known and 45 new sequence variations occurring 132 and 45 times, respectively. We found 6 somatic nucleotide changes in 5 out of the 8 chromophobe RCCs. One A --> T substitution occurred in the D-loop region and an insertion of a 9-bp sequence in the noncoding region of the MTNC7. One G --> A substitution and one C --> T substitution were seen in the MTRNR1 and MTRNR2 genes, respectively. One C deletion in MTND5 and one T insertion in the MTND3 gene resulted in frameshift mutations in two tumors. All somatic alterations, with the exception of the 9-bp insertion, were heteroplasmic changes. Although somatic mtDNA mutations are found in chromophobe RCCs, their role in the maintenance of tumor cell phenotype or in tumorigenesis remains to be elucidated.