EZH2 Codon 641 Mutations in Chinese Follicular Lymphoma Patients
Shuangping Guo, John KC Chan, Kai Fu, Bin Meng, Javeed Iqbal, Timothy McKeithan, Ruian Wang, Timothy C Greiner, Wing C Chan. Xi Jing Hospital, the Fourth Military Medical University, Xi'an, Shaan Xi, China; Queen Elizabeth Hospital, Hong Kong, China; University of Nebraska Medical Center, Omaha, NE; Qi Lu Hospital, Shan Dong Medical University, Jinan, Shan Dong Province, China
Background: Enhancer of zest homolog 2(EZH2) gene, the catalytic component of the polycomb repressive complex-2(PRC2), encodes a histone methyltransferase. Hemizygous mutations of EZH2 codon 641 lead to enhanced trimethylation of histone H3K27, were reported recently to occur frequently in diffuse large B-cell lymphomas, GCB type and follicular lymphomas (FLs). However, the frequency of EZH2 gene mutation in Chinese FLs is not known.
Design: We determined all the known variants of EZH2 codon 641 mutations in Chinese FLs cases (n=124) using Pyrosequencing, and compared them with Western FL cases (n=99). The sensitivity of the assay was determined to be at 5% of the genomic DNA of the cell line SU-DHL-6 harboring EZH2 codon Y641N mutation.
Results: All detected mutations were validated by another independent assay. The frequency of EZH2 gene mutation in FLs with or without BCL2 rearrangement was also analyzed. Our results showed that the frequency of EZH2 codon 641 mutations in Chinese FLs was similar to that of Western cohort (16.9% vs 20.2%). All of the five reported mutations, Y641F, Y641S, Y641C, Y641H and Y641N were detected in Chinese FLs with frequencies similar to previously reported Western FLs. Y641F was the most common mutation accounting for 38% of mutants, with decreasing frequencies from Y641S (24%), Y641H (14%), Y641C (14%) to Y641N (10%). No novel mutations were identified. EZH2 mutation frequency was higher in low morphologic grade FLs (Grade 1-2, 23.6% versus Grade 3, 7.7%). We also found that the frequencies of EZH2 mutation were significantly higher in FLs with BCL2-rearrangement in both Chinese and Western cohorts than those lacking BCL2 rearrangement (27.3% and 25.6% versus 7.7% and 9.7%) respectively.
Conclusions: EZH2 codon 641 mutations in Chinese FLs occurred at similar frequencies to Western FLs and it is more frequent in cases with BCL2 rearrangement. This mutation probably play a similar role in the pathogenesis of FLs in both Chinese and Western patients.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 252, Tuesday Afternoon