ABSTRACT. Levels of mtDNA⁴⁹⁷⁷ deletions (DmtDNA⁴⁹⁷⁷) have been found to be lower in tumors than in adjacent non-tumoral tissues. In 87 cancer patients, DmtDNA⁴⁹⁷⁷ was detected by multiplex polymerase chain reaction (PCR) amplification in 43 (49%) of the tumors and in 74 (85%) of the samples of non-tumoral tissues that were adjacent to the tumors. DmtDNA⁴⁹⁷⁷ deletions were detected in 24% of the breast tumors, 52% of the colorectal tumors, 79% of the gastric tumors, and 40% of the head and neck tumors as compared with 77, 83, 100, and 90% of the adjacent respective non-tumoral tissues at the same DNA template dilution. Based on limiting dilution PCR of 16 tumors and their adjacent non-tumoral tissues, it was found that the amount of DmtDNA⁴⁹⁷⁷ was 10- to 100-fold lower in the tumor than in the respective control non-tumoral tissues. Real-time PCR experiments were performed to quantify the number of DmtDNA⁴⁹⁷⁷ deletions per cell, by determining the mitochondrial-to-nuclear DNA ratio. In all of the cases of breast, colorectal, gastric, and head and neck cancer the proportion of DmtDNA⁴⁹⁷⁷ in tumors was lower than that of the respective non-tumoral tissue. Traces of DmtDNA⁴⁹⁷⁷ in tumors were apparently due to contamination of tumor tissue with surrounding non-tumoral tissue, as evidenced by tumor microdissection and in situ PCR techniques, suggesting that tumors are essentially free of this mutation. Although the metabolic effect of DmtDNA⁴⁹⁷⁷ may be minimal in normal (non-tumor) tissue, in tissue under stress, such as in tumors, even low levels of DmtDNA⁴⁹⁷⁷ deletions may be intolerable.

Key words: Mitochondria, Mitochondrial DNA, In situ PCR, Cancer, Kerns-Sayre syndrome deletion mutation, DmtDNA⁴⁹⁷⁷, Real-time PCR