diffuse large B-cell lymphomas; hypermethylation; prognosis; tumor suppressor genes
Abstract :
[en] Background: Diffuse large B-cell lymphoma (DLBCL) exhibits heterogeneous clinical features and a marked variable
response to treatment.
Patients and methods: 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 Prognostic Index (IPI), the germinal center immunophenotype, and 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.
Results: 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 a performance status
of two or more (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 remains an
independent prognostic factor in predicting shortened OS (P = 0.001) and DFS (P = 0.024), as well as the IPI and the
germinal center status.
Conclusions: This study 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 that may be used in conjunction with the conventional prognostic factors such as
the IPI and the germinal center status.
Research center :
Departments of Pathology and Clinical Hematology, Farhat-Hached Hospital of Sousse, Tunisia
Disciplines :
Hematology
Author, co-author :
Amara, Khaled
Trimeche, Mounir
Ziadi, Sonia
Laatiri, Adnen
Hachana, Mohamed Ridha ; Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Korbi, Sadok
Language :
English
Title :
Prognostic significance of aberrant promoter hypermethylation of CpG islands in patients with diffuse large B-cell lymphomas
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