Somatic mitochondrial DNA mutations in human chromophobe renal cell carcinomas

Abstract

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.

Mitochondrial DNA mutations in renal cell carcinomas revealed no general impact on energy metabolism

“…The mtDNA was more frequently mutated in renal carcinoma than in kidney cortex tissues. This is in line with somatic mtDNA mutations reported in a wide variety of human neoplasias (Fliss et al, 2000;Jones et al, 2001;Nagy et al, 2002;Tan et al, 2002). Somatic mutations in coding regions of the mtDNA in tumour tissues are either silent or mostly nonpathogenic polymorphisms.…”

“…Recently, a high incidence of specific mtDNA alterations has been reported for gastric (Maximo et al, 2001;Wu et al, 2005), prostate (Jeronimo et al, 2001;Petros et al, 2005), pancreatic (Jones et al, 2001), skin (Girald-Rosa et al, 2005), colorectal (Polyak et al, 1998;Hibi et al, 2001a;Lievre et al, 2005), urinary bladder (Fliss et al, 2000), thyroid (Yeh et al, 2000), oesophageal (Hibi et al, 2001b;Kumimoto et al, 2004), liver (Nishikawa et al, 2001), breast (Richard et al, 2000;Tan et al, 2002;Zhu et al, 2005), uterine cancers (Pejovic et al, 2004) as well as chromophobe renal cell carcinoma (Nagy et al, 2002). Of all mtDNA mutations reported in cancer tissues, only a few are known to be of pathological relevance as shown for patients with disorders of the mitochondrial energy metabolism.…”

Mitochondrial Resequencing Arrays Detect Tumor-Specific Mutations in Salivary Rinses of Patients with Head and Neck Cancer

“…Initial studies of body fluid detection of tumor-specific mitochondrial mutations in pancreatic juice and urine presented were promising, but our follow-up studies in pancreatic juices did not reflect the findings presented. 4 A single study has attempted an algorithm-based approach to quantitate the proportion of a heteroplasmic population of mitochondrial DNA which is comprised by a minor allele (19). This technique used a summation of the probe intensities of both the sense and antisense strands at a given mitochondrial position and assessed heteroplasmy (what we term the secondary base percentage) using the difference of the secondary base probe intensity from the lowest base probe intensity and quantitating heteroplasmy of this proportion compared with the primary base probe height.…”

Mitochondrial DNA mutations in human cancer

“…One-third (28%) of the sequence variants were reported in the D-loop region. (Nagy et al, 2002). Loss of mtDNA and the mRNA coding for NADH dehydrogenase subunit 3 was reported in eight of 13 tumor kidney tissues in another study (Selvanayagam and Rajaraman, 1996).…”