Less DeltamtDNA4977 than normal in various types of tumors suggests that cancer cells are essentially free of this mutation.
Less DeltamtDNA4977 than normal in various types of tumors suggests that cancer cells are essentially free of this mutation.
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发表时间：
2004-09
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通讯作者：
M. Dani;S. U. Dani;Silmara P G Lima;Alfredo Martínez;B. Rossi;F. Soares;M. Zago;A. Simpson
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作者：
M. Dani;S. U. Dani;Silmara P G Lima;Alfredo Martínez;B. Rossi;F. Soares;M. Zago;A. Simpson
MtDNA(4977)缺失(DelTamtDNA(4977))在肿瘤中的水平被发现低于邻近的非肿瘤组织。在87例肿瘤患者中，43例(49%)肿瘤组织和74例(85%)癌旁非肿瘤组织中检测到DelTamtDNA(4977)。在相同的DNA模板稀释度下，24%的乳腺肿瘤、52%的结直肠肿瘤、79%的胃肿瘤和40%的头颈部肿瘤中检测到DelTamtDNA(4977)缺失，而在邻近的非肿瘤组织中分别检测到77%、83%、100和90%的DelTamtDNA缺失。对16例肿瘤及癌旁组织进行限制性稀释聚合酶链式反应，发现肿瘤组织中DelTamtDNA(4977)的量比相应的对照非肿瘤组织低10~100倍。实时定量聚合酶链式反应实验通过测定线粒体与核DNA的比率来量化每个细胞中DelTamtDNA(4977)缺失的数量。在所有乳腺癌、结直肠癌、胃癌和头颈癌中，肿瘤组织中DelTamtDNA的比例(4977)低于相应的非肿瘤组织。肿瘤显微解剖和原位聚合酶链式反应技术证实，肿瘤组织中的DelTamtDNA(4977)明显是由于肿瘤组织与周围非肿瘤组织的污染所致，表明肿瘤基本上没有这种突变。尽管DelTamtDNA(4977)对正常(非肿瘤)组织的代谢影响可能很小，但在承受压力的组织中，如肿瘤，即使低水平的DelTamtDNA(4977)缺失也可能是不可容忍的。
Levels of mtDNA(4977) deletions (DeltamtDNA(4977)) have been found to be lower in tumors than in adjacent non-tumoral tissues. In 87 cancer patients, DeltamtDNA(4977) 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. DeltamtDNA(4977) 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 DeltamtDNA(4977) 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 DeltamtDNA(4977) 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 DeltamtDNA(4977) in tumors was lower than that of the respective non-tumoral tissue. Traces of DeltamtDNA(4977) 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 DeltamtDNA(4977) may be minimal in normal (non-tumor) tissue, in tissue under stress, such as in tumors, even low levels of DeltamtDNA(4977) deletions may be intolerable.