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Methylation status of fragile histidine triad ( FHIT ) gene and its clinical impact on prognosis of patients with multiple myeloma
Author(s) -
Takada Satoru,
Morita Kimio,
Hayashi Kunihiko,
Matsushima Takahumi,
Sawamura Morio,
Murakami Hirokazu,
Nojima Yoshihisa
Publication year - 2005
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2005.00560.x
Subject(s) - multiple myeloma , fhit , methylation , triad (sociology) , medicine , oncology , cancer research , gene , genetics , bioinformatics , biology , psychology , cancer , tumor suppressor gene , carcinogenesis , psychoanalysis
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 (≤8.5 g/dL, P = 0.007), hypoalbuminemia (≤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.