title: Reduced mRNA and protein expression of the genomic caretaker RAD9A in primary fibroblasts of individuals with childhood and independent second cancer.
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.
  
  
  RESULTS
  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 γ-irradiated cells of two-cancer patients.
  
  
  CONCLUSIONS
  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.
authors: Institute of Human Genetics, University Medical Center, Mainz, Germany.
authors: Eva
authors: E
authors: Weis
authors: Holger
authors: H
authors: Schoen
authors: Anja
authors: A
authors: Victor
authors: Claudia
authors: C
authors: Spix
authors: Marco
authors: M
authors: Ludwig
authors: Brigitte
authors: B
authors: Schneider-Raetzke
authors: Nicolai
authors: N
authors: Kohlschmidt
authors: Oliver
authors: O
authors: Bartsch
authors: Aslihan
authors: A
authors: Gerhold-Ay
authors: Nils
authors: N
authors: Boehm
authors: Franz
authors: F
authors: Grus
authors: Thomas
authors: T
authors: Haaf
authors: Danuta
authors: D
authors: Galetzka
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016609:Neoplasms, Second Primary / Q000235:genetics*; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D018797:Cell Cycle Proteins; D012333:RNA, Messenger; C069930:rad9 protein