Clinical significance of PCDH10 promoter methylation in diffuse large B-cell lymphoma.

BACKGROUND: PCDH10, one of the non-clustered protocadherins, is identified as a tumor suppressor gene in many tumors. Recently, promoter methylation of PCDH10 was found in diffuse large B-cell lymphoma (DLBCL) but not in normal lymph nodes, suggesting that its epigenetic aberrance is essential to the lymphomagenesis. However, there are few studies on the clinicopathological relevance and prognostic significance of PCDH10 methylation status in DLBCL.

METHODS: One hundred-seven cases of DLBCL between Jan 2009 and Jul 2010 were selected to extract genomic DNA and perform bisulfite modification. Their methylation status of PCDH10 promoter were accessed by methylation-specific PCR (MSP) with methylated and unmethylated primers. Analysis of overall survival and clinicopathological correlation were conducted.

RESULTS: PCDH10 hypermethylation were found in 54.2% (58/107) of DLBCL cases, but only 12.5% (1/8) in reactive lymph node/follicular hyperplasia. In RCHOP-treated cohort, promoter methylation of PCDH10 is an independent prognostic indicator of worse overall survival (p = 0.017; HR 4.045; 95%CI 1.287-12.711) and worse progress-free survival (p = 0.014; HR 2.977; 95%CI 1.245-7.119). Whereas, PCDH10 hypermethylation wasn't correlated with MYC translocation and cell of origin classification using Hans model.

CONCLUSIONS: PCDH10 methylation status could serve as a valuable biomarker for risk classification, and a potential therapeutic target for demethylating drugs in DLBCL in the future.