Identification of genetic defect coupled with the susceptibility to childhood leukemia

鉴定与儿童白血病易感性相关的遗传缺陷

• 批准号: 17591116
• 负责人: SHIMADA Hiroyuki
• 金额: $ 1.34万
• 依托单位: KEIO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591116/
• 关键词: Pediatric Cancer; Susceptibility; SNP; DNA repair gene; Apoptosis

Factors affected the susceptibility of pediatric malignant diseases may be innate phenomena. To explore this possibility, we tried a unique approach to analyze genetical and biological feature of lymphoblast cells established from the patients with childhood leukemia. Cells from the patients displayed marked chromosomal instability ; changes in ploidy, translocations and breakages. We re-sequenced entire coding regions in the ATM, CHK2, and TP53 genes in patients and healthy samples. The mutations in them were found only in the patients. Expression profiling shows abnormal expression of apoptosis and repair related genes. The result suggests germ-line defect(s) in repair or apoptosis pathways leads chromosomal aberrations and resulted in malignant transformation.

影响小儿恶性病的敏感性的因素可能是先天现象。为了探索这种可能性，我们尝试了一种独特的方法来分析由儿童白血病患者确定的淋巴细胞细胞的遗传和生物学特征。来自患者的细胞表现出明显的染色体不稳定性；倍增，易位和破裂的变化。我们在ATM，CHK2和TP53基因和健康样本中重新列出了ATM，CHK2和TP53基因的整个编码区域。它们中的突变仅在患者中发现。表达谱图显示凋亡和修复相关基因的异常表达。结果表明，修复或凋亡途径中的种系缺陷会导致染色体畸变，并导致恶性转化。