title: 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.
authors.affiliation: Department of Internal Medicine, National Nishi Gunma Hospital, Shibukawa, Japan. s-takada@maebashi.saiseikai.or.jp
authors.forename: Satoru
authors.initials: S
authors.lastname: Takada
authors.forename: Kimio
authors.initials: K
authors.lastname: Morita
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Takahumi
authors.initials: T
authors.lastname: Matsushima
authors.forename: Morio
authors.initials: M
authors.lastname: Sawamura
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Murakami
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nojima
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D034141:Hypoalbuminemia / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000401:mortality; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012737:Sex Factors; D001613:beta 2-Microglobulin / Q000097:blood; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D014408:Biomarkers, Tumor; D002097:C-Reactive Protein; D009363:Neoplasm Proteins; D001613:beta 2-Microglobulin; D000099170:Bis(5'-adenosyl)triphosphatase