Methylation status of fragile histidine triad (FHIT) gene and its clinical impact on prognosis of patients with multiple myeloma

Abstract

Aberrant methylation of tumor suppressor genes (TSG) has been studied in multiple myeloma (MM). We determined the methylation status of the FHIT (fragile histidine triad) gene, a putative TSG, in 48 patients with MM. Clinical association with its methylation status was then analyzed. The FHIT gene methylation was observed in 21 of the 48 patients (44%). No association between FHIT gene methylation and clinical variables such as age, gender and clinical stage was found. However, the estimated 50% survival time of the methylated group was significantly shorter than that of the unmethylated group (18.2 vs. 45.1 months, P < 0.05). Univariate analysis revealed adverse prognostic factors: FHIT gene methylation (P = 0.028), poor performance status (I to IV, P = 0.002), anemia (< or =8.5 g/dL, P = 0.007), hypoalbuminemia (< or =3.5 g/dL, P < 0.002), high serum C-reactive protein levels (>0.5 mg/dL, P = 0.002), elevated beta-2-microglobulin serum levels (>6.5 mg/L, P < 0.001), and treatments not including autologous peripheral blood stem cell transplantation (auto-PBSCT) (P = 0.007). Multivariate analysis identified FHIT gene methylation [hazard ratio (HR) 1.722, 95% confidence interval (CI) 1.150-2.603, P = 0.009], elevated beta-2-microglobulin serum levels (>6.5 mg/L, HR 2.005, 95% CI 1.035-3.937, P = 0.004), and treatments not including auto-PBSCT are independent predictive variables. These findings indicate that aberrant methylation of the FHIT gene is an independent adverse prognostic factor in MM.

The clinicopathological significance of FHIT hypermethylation in non-small cell lung cancer, a meta-analysis and literature review

“…Our studies searched 9 studies which included 1077 patients. A number of studies showed that inactivation of FHIT can cause tumor aberrant progression and link to clinicopathological characteristics 27 48 49 50 51 . Therefore, FHIT can be considered as a tumor suppressor, and its inactivation could contribute tumor progression and poor prognosis.…”

The clinicopathological significance and ethnic difference of FHIT hypermethylation in non-small-cell lung carcinoma: a meta-analysis and literature review

“… 55 A number of studies showed that inactivation of FHIT can cause tumor aberrant progression and link to clinicopathological characteristics. 28 , 38 , 56 – 58 Therefore, FHIT can be considered as a tumor suppressor, and its inactivation could contribute to tumor progression and poor prognosis. Although only four studies evaluated the relationship between OS and FHIT hypermethylation in NSCLC, they showed very similar results.…”

Decitabine enhances bortezomib treatment in RPMI 8226 multiple myeloma cells

“…In MM, DNA methylation is important for the pathogenesis, progression and prognosis of the disease. Previous studies have suggested that numerous genes are hypermethylated in MM, including glutathione peroxidase 3, retinol binding protein 1, secreted protein acidic and cysteine rich, transforming growth factor β induced, cyclin-dependent kinase inhibitor 2A, suppressor of cytokine signaling 1, fragile histidine triad 1, death associated protein kinase 1 and transforming growth factor β receptor 2 (34)(35)(36)(37)(38). Therefore, targeting DNA methylation may permit optimized therapy for MM, which warrants further investigation.…”