Genetic factors are important for developing primary and subsequent malignancies in children. This study investigated the role of genetic factors involved in DNA-repair. Designed as a feasibility study, it addressed the possibility of obtaining samples for genetic analyses from former patients through the German Childhood Cancer Registry. Testing feasibility was as important as the biological question itself. We analyzed the expression of DNA-repair genes in untreated primary fibroblasts of 20 individuals with a second neoplasm compared to 20 matched single neoplasm cases using customized cDNA microarrays (1344 gene sequences, about 800 genes). Matching was by first neoplasm, age, and year of first diagnosis. Forty-six percent of the 52 contacted second neoplasm cases and 18% of the 132 single neoplasm patients participated in the study. The DNA-repair gene results show small differences in the basal gene expression of FTH1 and CDKN1A. To our knowledge, this is the first study using gene expression arrays in untreated primary fibroblasts regarding second neoplasms after a childhood neoplasm. We were able to recruit childhood cancer patients for genetic analyses long after diagnosis. The biological importance of the differences in the DNA-repair gene expression has to be elucidated yet.

译文

:遗传因素对于发展儿童原发性和随后的恶性肿瘤很重要。这项研究调查了遗传因素在DNA修复中的作用。作为一项可行性研究而设计,它解决了通过德国儿童癌症登记处从以前的患者那里获得用于基因分析的样本的可能性。测试的可行性与生物学问题本身一样重要。我们使用定制的cDNA微阵列(1344个基因序列,约800个基因)分析了20个具有第二个肿瘤的个体的未修复原代成纤维细胞与20个匹配的单个肿瘤病例相比的DNA修复基因的表达。匹配的依据是首次肿瘤,年龄和首次诊断的年份。在52例接触的第二肿瘤病例中,有46%参与了研究,在132例单发肿瘤患者中,有18%参与了研究。 DNA修复基因结果显示FTH1和CDKN1A的基础基因表达有微小差异。就我们所知,这是第一项在未治疗的原代成纤维细胞中使用基因表达阵列的研究,涉及童年肿瘤之后的第二次肿瘤。诊断后很长一段时间,我们就能够招募儿童期癌症患者进行基因分析。 DNA修复基因表达差异的生物学重要性尚未阐明。

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