Identification of genetic defect coupled with the susceptibility to childhood leukemia

影响小儿恶性疾病易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从儿童白血病患者身上建立的淋巴母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；倍性的改变，易位和断裂。我们重新测序了患者和健康样本中ATM、CHK2和TP53基因的整个编码区。它们的突变只在病人身上发现。表达谱显示凋亡和修复相关基因的异常表达。结果表明，生殖系修复或凋亡途径的缺陷导致染色体畸变并导致恶性转化。

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.