Papaefthymiou Maria A, Giaginis Costas T, Theocharis Stamatios E
Department of Forensic Medicine and Toxicology, Medical School, University of Athens, Athens, Greece.
Med Sci Monit. 2008 Jan;14(1):RA8-15.
DNA repair is an important defense mechanism against DNA damage and includes four distinct pathways: direct, excision, mismatch, and double-strand break repair systems. Recent evidence suggests that alterations in proteins participating in the DNA repair systems may result in cellular senescence, cell death, and neoplastic transformation. Malignancies in adulthood exhibit genomic instability and an increased mutation rate due to underlying defects in DNA repair. However, our knowledge on DNA repair defects, both in germline and somatic mutations, and their relationship with childhood malignancies remains incomplete. Mutations, gene deletions, and inversions in various DNA repair genes have been reported and special attention has recently been focused on the interaction between these abnormalities and malignant transformation in childhood. The purpose of this review is to summarize the existing clinical information concerning components of the DNA repair systems and their influence on the development of the most common pediatric malignancies, including leukemia, tumors of the central nervous system, rhabdomyosarcoma, and retinoblastoma. Such information could possibly explain the response or resistance to chemotherapy and the possible risk of relapse in childhood malignancies presenting specific DNA repair defects. Additionally, these data could be beneficial for the development of novel therapeutic strategies.
DNA修复是抵御DNA损伤的重要防御机制，包括四种不同的途径：直接修复、切除修复、错配修复和双链断裂修复系统。最近的证据表明，参与DNA修复系统的蛋白质发生改变可能导致细胞衰老、细胞死亡和肿瘤转化。成年期的恶性肿瘤由于DNA修复存在潜在缺陷而表现出基因组不稳定和突变率增加。然而，我们对种系和体细胞突变中的DNA修复缺陷及其与儿童恶性肿瘤的关系的了解仍然不完整。已经报道了各种DNA修复基因中的突变、基因缺失和倒位，最近特别关注这些异常与儿童恶性转化之间的相互作用。本综述的目的是总结有关DNA修复系统组成部分的现有临床信息，以及它们对最常见儿童恶性肿瘤（包括白血病、中枢神经系统肿瘤、横纹肌肉瘤和视网膜母细胞瘤）发生发展的影响。这些信息可能有助于解释对化疗的反应或耐药性，以及存在特定DNA修复缺陷的儿童恶性肿瘤复发的可能风险。此外，这些数据可能有利于新治疗策略的开发。
