Research Article

Less DmtDNA4977 than normal in various types of tumors suggests that cancer cells are essentially free of this mutation

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.

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.

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