TY  - JOUR
A1  - Weis, Eva
A1  - Schoen, Holger
A1  - Victor, Anja
A1  - Spix, Claudia
A1  - Ludwig, Marco
A1  - Schneider-Raetzke, Brigitte
A1  - Kohlschmidt, Nicolai
A1  - Bartsch, Oliver
A1  - Gerhold-Ay, Aslihan
A1  - Boehm, Nils
A1  - Grus, Franz
A1  - Haaf, Thomas
A1  - Galetzka, Danuta
T1  - Reduced mRNA and Protein Expression of the Genomic Caretaker RAD9A in Primary Fibroblasts of Individuals with Childhood and Independent Second Cancer
JF  - PLoS ONE
N2  - 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 screened primary fibroblasts of matched patients for differences in the amount of representative DNA repair-associated proteins. We found constitutively decreased levels of RAD9A and several other DNA repair proteins in two-cancer patients, compared to one-cancer patients. The RAD9A protein level increased in response to DNA damage, however to a lesser extent in the two-cancer patients. Quantification of mRNA expression by real-time RT PCR revealed lower RAD9A mRNA levels in both untreated and 1 Gy gamma-irradiated cells of two-cancer patients. 

Conclusions/Significance: 

Collectively, our results support the idea that modulation of RAD9A and other cell cycle arrest and DNA repair proteins contribute to the risk of developing a second malignancy in childhood cancer patients.
KW  - DNA methylation
KW  - Malignant neoplasms
KW  - Genes
KW  - Instability
KW  - Stability
KW  - Susceptibility
KW  - Checkpoints
KW  - Repair
KW  - Damage
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141838
VL  - 6
IS  - 10
ER  - 
TY  - JOUR
A1  - Weis, Eva
A1  - Schoen, Holger
A1  - Victor, Anja
A1  - Spix, Claudia
A1  - Ludwig, Marco
A1  - Schneider-Raetzke, Brigitte
A1  - Kohlschmidt, Nicolai
A1  - Bartsch, Oliver
A1  - Gerhold-Ay, Aslihan
A1  - Boehm, Nils
A1  - Grus, Franz
A1  - Haaf, Thomas
A1  - Galetzka, Danuta
T1  - Reduced mRNA and Protein Expression of the Genomic Caretaker RAD9A in Primary Fibroblasts of Individuals with Childhood and Independent Second Cancer
N2  - 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 screened primary fibroblasts of matched patients for differences in the amount of representative DNA repair-associated proteins. We found constitutively decreased levels of RAD9A and several other DNA repair proteins in two-cancer patients, compared to onecancer patients. The RAD9A protein level increased in response to DNA damage, however to a lesser extent in the twocancer patients. Quantification of mRNA expression by real-time RT PCR revealed lower RAD9A mRNA levels in both untreated and 1 Gy c-irradiated cells of two-cancer patients. Conclusions/Significance: Collectively, our results support the idea that modulation of RAD9A and other cell cycle arrest and DNA repair proteins contribute to the risk of developing a second malignancy in childhood cancer patients.
KW  - Medizin
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-74777
ER  -