Functional, genetic, and epigenetic aspects of base and nucleotide excision repair in colorectal carcinomas.

نویسندگان

  • Jana Slyskova
  • Vlasta Korenkova
  • Andrew R Collins
  • Pavel Prochazka
  • Ludmila Vodickova
  • Jiri Svec
  • Ludmila Lipska
  • Miroslav Levy
  • Michaela Schneiderova
  • Vaclav Liska
  • Lubos Holubec
  • Rajiv Kumar
  • Pavel Soucek
  • Alessio Naccarati
  • Pavel Vodicka
چکیده

PURPOSE DNA repair capacity (DRC) is a determinant not only of cancer development but also of individual response to therapy. Previously, altered base and nucleotide excision repair (BER and NER) have been described in lymphocytes of patients with sporadic colorectal cancer. We, for the first time, evaluate both excision repair capacities in human colon biopsies to study their participation in colorectal tumorigenesis. EXPERIMENTAL DESIGN Seventy pairs of tumor and adjacent healthy tissues were analyzed for BER- and NER-specific DRC by a comet repair assay. Tissue pairs were further compared for expression levels of a panel of 25 BER and NER genes complemented by their promoter methylation status. RESULTS We observed a moderate increase of NER-DRC (P = 0.019), but not of BER-DRC in tumors. There was a strong correlation between both tissues for all investigated parameters (P < 0.001). However, 4 NER (CSB, CCNH, XPA, XPD) and 4 BER (NEIL1, APEX1, OGG1, PARP1) genes showed a 1.08- to 1.28-fold change difference in expression in tumors (P < 0.05). Individual gene expression levels did not correlate with overall DRC, and we did not detect any aberrant methylation of the investigated genes. CONCLUSIONS Our complex analysis showed that tumor cells are not deficient in BER and NER, but rather follow patterns characteristic for each individual and are comparable with adjacent tissue. Alteration of excision repair pathways is not a pronounced event in colorectal carcinogenesis. This study shows the feasibility of DRC evaluation in human solid tissues, representing a complex marker of multigene DNA repair processes.

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Human Cancer Biology Functional, Genetic, and Epigenetic Aspects of Base and Nucleotide Excision Repair in Colorectal Carcinomas

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عنوان ژورنال:
  • Clinical cancer research : an official journal of the American Association for Cancer Research

دوره 18 21  شماره 

صفحات  -

تاریخ انتشار 2012