Absence of methylation-dependent transcriptional silencing in TP73 irrespective of the methylation status of the CDKN2A CpG island in plasma cell neoplasia

• Published in: Leukemia research 2009-09, Vol.33 (9), p.1272-1275
• Main Authors: Hatzimichael, Eleftheria, Benetatos, Leonidas, Dasoula, Aggeliki, Dranitsaris, George, Tsiara, Stavroula, Georgiou, Ioannis, Syrrou, Maria, Stebbing, Justin, Coley, Helen M, Crook, Tim, Bourantas, Konstantinos L
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Base Sequence; CDKN2A; CpG Islands; DNA Methylation; DNA Primers; DNA-Binding Proteins - genetics; Female; Gene Silencing; Genes, p16; Hematology, Oncology and Palliative Medicine; Humans; Male; Methylation; Middle Aged; Multiple myeloma; Multiple Myeloma - genetics; Nuclear Proteins - genetics; Promoter Regions, Genetic; TP73; Transcription, Genetic; Tumor Protein p73; Tumor Suppressor Proteins - genetics; Waldenstrom Macroglobulinemia - genetics; Waldenström's macroglobulinemia
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2009.04.009

Abstract Few studies exist regarding the methylation status of the TP73 CpG island in plasma cell dyscrasias. We have tested whether CpG methylation of both CDKN2A and TP73 occurs in 45 individuals with multiple myeloma (24 male and 21 female, mean age 66.4 years) and in 4 patients (2 male and 2 female, mean age 61.7 years) with Waldenström's macroglobulinemia. No patient was found to be methylated for the promoter of TP73 while CDKN2A promoter was found to be methylated in 12/45 MM patients (26.6%) at diagnosis and in 1/4 WM patients. To verify the absence of detectable methylation observed using MSP, we performed bisulphite sequence analysis on a subset of the cases and confirmed the absence of methylation. Interesting trends were identified where patients with methylated CDKN2A had an increased risk of death (HR = 1.9, p = 0.32), advanced stage disease (DS ≥ II) (OR = 1.9, p = 0.3) and anemia (OR = 1.4, p = 0.6). TP7 3 CpG methylation is an infrequent event in patients with MM and WM. Further evaluation in a larger sample of patients is needed in order to enhance our statistical power and to test our hypothesis that CDKN2A methylation status can become a useful prognostic biomarker.