DETECTION OF MITOCHONDRIAL GENOME DEPLETION BY A NOVEL CDNA IN RENAL-CELL CARCINOMA

A cDNA isolated by a subtractive hybridization procedure detected loss of mtDNA and the mRNA coding for NADH dehydrogenase subunit 3 in 8 of 13 tumor kidney tissues obtained from patients with renal cell carcin oma. Sequencing revealed a stretch of nucleotides homologous to the mi tochondrial NADH dehydrogenase subunit 3 gene in the middle of the cDN A. The depletion phenomenon was also observed in five of six renal car cinoma cell lines. In the case of a benign renal oncocytoma, however, the mtDNA content was increased 200% more than that of the adjacent no rmal tissue. The frequency with which this phenomenon occurs in renal cell carcinomas, but not in other types of cancers, suggests that this may be an important phenotype associated with renal cell neoplastic t ransformation. However, the absence of any structural alterations with in the mitochondrial genome suggests that the depletion may be a secon dary event associated with the oncogenic transformation process.