Methylation status of fragile histidine triad (FHIT) gene and its clinical impact on prognosis of patients with myelodysplastic syndrome.

ABSTRACT

The fragile histidine triad (FHIT) gene plays an important role in anti-cancer and the abnormal methylation of FHIT gene is found in many carcinomas. The epigenetic changes of tumor suppressor genes (TSG) are now recognized as an abnormal mechanism contributing to the development of myelodysplastic syndrome (MDS). To clarify the role of FHIT in MDS, we examined the methylation status of FHIT in patients with MDS. Methylation-specific polymerase (MSP) chain reaction was performed to detect the aberrant promoter methylation of FHIT gene in 55 patients with MDS. The abnormal methylation of the FHIT gene was found in 26 of 55 (47.2%) MDS cases, but it was not in normal control. No relationship was found between FHIT gene methylation and sex, hematologic parameters, chromosomal abnormalities of MDS patients. However, the significant difference was observed in the frequencies of FHIT gene hypermethylation among patients with RA/RARS (7/25, 28.0%), RAEB (11/18, 61.1%) and RAEBt (8/11, 72.7%) (chi2 value=7.938, P=0.019). Furthermore, there was a positive correlation between the frequency of FHIT gene hypermethylation and different IPSS groups (chi2 value=10.110, P=0.018). The MDS patients with FHIT gene methylation had significantly shorter survival time than those without FHIT methylation (20.0 months vs. 40.0 months, P=0.025). These results suggested that aberrant methylation of the FHIT gene might be one of molecular events involved in the disease progression of MDS and be an adverse prognostic factor in MDS.