A79
Aberrant promoter hypermethylation of DAPK gene is an independent prognostic factor in patients with diffuse large B-cell lymphomas
Khaled Amara1, Mounir Trimeche1, Sonia Ziadi1, Adnene Laatiri2, Mohamed Hachana1, Sarra Mestiri1, Sadok Korbi1
1CHU Farhat Hached. Department of Pathology, Sousse, Tunisia, 2CHU Farhat Hached. Department of Clinical Hematology, Sousse, Tunisia
Diffuse large B-cell lymphoma (DLBCL) exhibits heterogeneous clinical features and a marked variable response to treatment. In this study we investigated the prognostic significance of the methylation status of DAPK, GSTP1, P14, P15, P16, P33, RB1, SHP1, CDH1, APC, BLU, VHL, TIMP3, and RASSF1A genes in 46 DLBCL specimens from Tunisian patients. Methylation status of each gene was correlated with clinicopathological parameters including the International Prognosis Index (IPI), response to treatment and survival. Overall survival (OS) and disease-free survival (DFS) rates were calculated by the Kaplan–Meier method and differences were compared with the log-rank test.
Hypermethylation of SHP1 was associated with elevated lactate dehydrogenase level (P=0.031). P16 and VHL were frequently hypermethylated in patients with high IPI scores (P=0.006 and 0.004) and performance status ≥2 (P=0.007 and 0.047). In addition, hypermethylation of P16 was significantly associated with advanced clinical stages and B symptoms (P=0.041 and 0.012). Interestingly, hypermethylation of DAPK was significantly correlated with resistance to treatment (P=0.023). With regard to survival rates, promoter hypermethylation of DAPK, P16, and VHL were significantly associated with shortened OS (P=0.003, 0.001, and 0.017, respectively) and DFS (P=0.006, 0.003, and 0.046, respectively). In multivariate analysis, hypermethylation of DAPK remain an independent prognostic factor in predicting shortened OS (P=0.001) and DFS (P=0.024).
Thisstudy demonstrates that DLBCLs with hypermethylated P16, VHL, DAPK, and SHP1 commonly show a biologically aggressive phenotype and worse prognosis. Interestingly, hypermethylation of DAPK was found to be an independent prognostic factor for OS and DFS in DLBCLs.
