Anti-FHIT (aa 25-147) polyclonal antibody

Chromosomal positions of common fragile sites differ in lymphoblasts and fibroblasts, with positions dependent on the epigenetically determined density of replication origins at these loci. Because rearrangement of fragile loci and associated loss of fragile gene products are hallmarks of cancers, we aimed to map common fragile sites in epithelial cells, from which most cancers derive. Among the five most frequently activated sites in human epithelial cells were chromosome bands 2q33 and Xq22.1, which are not among top fragile sites identified in lymphoblasts or fibroblasts. FRA16D at 16q23 was among the top three fragile sites in the human epithelial cells examined, as it is in lymphoblasts and fibroblasts, while FRA3B at 3p14.2, the top fragile locus in lymphoblasts, was not fragile in most epithelial cell lines tested. Epithelial cells exhibited varying hierarchies of fragile sites; some frequent epithelial cell fragile sites are apparently not frequently altered in epithelial cancers and sites that are frequently deleted in epithelial cancers are not necessarily among the most fragile. Since we have reported that loss of expression of the FRA3B-encoded FHIT protein causes increased replication stress-induced DNA damage, we also examined the effect of FHIT-deficiency on markers of genome instability in epithelial cells. FHIT-deficient cells exhibited increases in fragile breaks and in H2AX and 53BP1 foci in G1 phase cells, confirming in epithelial cells that the FHIT gene and encompassing FRA3B, is a caretaker gene necessary for maintenance of genome stability. (c) 2013 Wiley Periodicals, Inc.

In our previous study, the 4-aminobutyrate aminotransferase (ABAT) gene was screened and selected as a target gene that may affect the prognosis of myelo-dysplastic syndrome (MDS). The present study aimed to determine the prognostic value of ABAT in 152 patients with MDS, 29 patients with acute myeloid leukemia (AML) and 40 controls, by detecting the expression and methylation levels of the ABAT gene. In patients with MDS, the expression levels of ABAT were significantly reduced compared with in the controls (P<0.0001), and the degree of DNA methylation was increased in MDS subjects (P<0.0001). Age, hemoglobin level, marrow blasts, International Prognostic Scoring System karyotype, and the expression and methylation levels of ABAT were associated with overall survival (OS), as determined by univariate analysis. Multivariate analysis revealed that older age, higher marrow blasts and higher methylation percentage were independent risk factors for OS. In addition, a functional study demonstrated that ABAT gene silencing increased cell apoptosis and blocked the G(1)/S phase in SKM-1 and THP-1 human leukemia cells. A -aminobutyrate aminotransferase inhibitor also blocked the G(1)/S phase; however, it had no effect on cell apoptosis. In conclusion, the present study demonstrated that ABAT methylation served an essential role in the progression of MDS and therefore may be considered an indicator of poor prognosis for hematological malignancies.