reduced mrna and protein expression of the genomic caretaker rad9a in primary fibroblasts of individuals with childhood and independent second cancer减少mrna和蛋白表达的主要成纤维细胞的基因组看守rad9a患者童年和独立第二癌症.pdfVIP

Reduced mRNA and Protein Expression of the Genomic Caretaker RAD9A in Primary Fibroblasts of Individuals with Childhood and Independent Second Cancer 1 1 2 2 1 1 Eva Weis , Holger Schoen , Anja Victor , Claudia Spix , Marco Ludwig , Brigitte Schneider-Raetzke , 1 1 2 3 3 4 Nicolai Kohlschmidt , Oliver Bartsch , Aslihan Gerhold-Ay , Nils Boehm , Franz Grus , Thomas Haaf *, Danuta Galetzka1 1 Institute of Human Genetics, University Medical Center, Mainz, Germany, 2 Institute of Medical Biometry, Epidemiology and Informatics, University Medical Center, Mainz, Germany, 3 Experimental Ophthalmology, Ocular Proteomics and Immunology Center, University Medical Center, Mainz, Germany, 4 Institute of Human Genetics, ¨ Julius Maximilians University, Wurzburg, Germany Abstract Background: The etiology of secondary cancer in childhood cancer survivors is largely unclear. Exposure of normal somatic cells to radiation and/or chemotherapy can damage DNA and if not all DNA lesions are properly fixed, the mis-repair may lead to pathological consequences. It is plausible to assume that genetic differences, i.e. in the pathways responsible for cell cycle control and DNA repair, play a critical role in the development of secondary cancer. Methodology/Findings: To identify factors that may influence the susceptibility for second cancer formation, we recruited 20 individuals who survived a childhood malignancy and then developed a second cancer as well as 20 carefully matched control individuals with childhood malignancy but without a second cancer. By antibody microarrays, we scr