Cancer cells are characterized by their ability to grow at an uncontrolled, quickened and indefinite pace. Point mutations in tumor suppressor genes and proto-oncogenes, changes in chromosome copy numbers and structure are various forms of genome instability that constitute a hallmark of cancer. Several studies suggest a strong correlation and molecular colocalization between cancer breakpoints and breaks at nonrandom genomic loci called common fragile sites (CFSs). This finding highlights the importance of CFSs in oncogenesis. CFSs are site-specific breaks that are observed on metaphase chromosomes when cells are cultured under stress conditions. They are found in all individuals and are mainly induced by low doses of aphidicolin (Aph), a partial inhibitor of DNA polymerases alpha, delta and epsilon. In this study, we propose to determine the expression frequency of FRAXB, a CFS located at Xp22.31 and one of the most CFS expressed in the human genome, in healthy persons of different ages. Blood samples from several donors were collected, cultured and lymphocytes were then treated with 0.2 µg/ml of Aph. RP11-483M24, a probe specific for FRAXB hotspot of breakage was used in FISH in order to detect FRAXB breaks. One hundred fluorescent signals were analyzed per donor using fluorescence microscopy. The results show that the percentage of breakage ranges from 6% to 25% with several folds increase among females in the twenties and from 3% to 19% among males of the same age suggesting the presence of CFS expression variability among individuals of the same age and gender. Such inter-individual variability in CFS bre akages could be due to personal difference in the genetic background and can explain why there is variability in cancer incidence among individuals with the same age subjected to the same environmental conditions and mutagens. This finding can be used as a biomarker for cancer prevention.
Cancer cells are characterized by their ability to grow at an uncontrolled, quickened and indefinite pace. Point mutations in tumor suppressor genes and proto-oncogenes, changes in chromosome copy numbers and structure are various forms of genome instability that constitute a hallmark of cancer. Several studies suggest a strong correlation and molecular colocalization between cancer breakpoints and breaks at nonrandom genomic loci called common fragile sites (CFSs). This finding highlights the importance of CFSs in oncogenesis. CFSs are site-specific breaks that are observed on metaphase chromosomes when cells are cultured under stress conditions. They are found in all individuals and are mainly induced by low doses of aphidicolin (Aph), a partial inhibitor of DNA polymerases alpha, delta and epsilon. In this study, we propose to determine the expression frequency of FRAXB, a CFS located at Xp22.31 and one of the most CFS expressed in the human genome, in healthy persons of different ages. Blood samples from several donors were collected, cultured and lymphocytes were then treated with 0.2 µg/ml of Aph. RP11-483M24, a probe specific for FRAXB hotspot of breakage was used in FISH in order to detect FRAXB breaks. One hundred fluorescent signals were analyzed per donor using fluorescence microscopy. The results show that the percentage of breakage ranges from 6% to 25% with several folds increase among females in the twenties and from 3% to 19% among males of the same age suggesting the presence of CFS expression variability among individuals of the same age and gender. Such inter-individual variability in CFS bre akages could be due to personal difference in the genetic background and can explain why there is variability in cancer incidence among individuals with the ...
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