Methylation of p16INK4A and mitotic arrest defective protein 2 (MAD2) genes in gastric marginal-zone B-cell lymphomas.
BACKGROUND
Products of cyclin-dependent kinase inhibitor p16(INK4A)and mitotic arrest defective protein 2 (MAD2) genesare key regulator proteins at the G1 restriction point and mitotic checkpoint of the cell cycle. The objective of this study was to investigate the role of promoter methylation of p16(INK4A) and MAD2 genes in gastric marginal-zone B-cell lymphoma (MZBCL).


METHODS
Gastric biopsies from 40 patients were analyzed by methylation-specific polymerase chain reaction, and the methylation status was compared with the results of BCL10 expression and t(11;18)(q21;q21) translocation.


CONCLUSIONS
p16(INK4A) was methylated in 30 of 40 MZBCLs (75%). The lymphomas with p16(INK4A) methylation tended to be negative for t(11;18)(q21;q21) (p = 0.011). MAD2 gene was methylated in 23 of 38 MZBCLs (61%). Lymphomas with MAD2 gene methylation more frequently expressed BCL10 (p = 0.037). These methylation profiles suggest that p16(INK4A) and MAD2 gene may play a role in the pathogenesis of MZBCL via different pathways; MAD2 gene is Helicobacter pylori independent with a close association with BCL10 while p16(INK4A) is H. pylori dependent with an inverse correlation with the t(11;18)(q21;q21) translocation.
Park
Sanghui
S
Department of Pathology, Gachon University of Medicine and Science, Gil Medical Center, Incheon, Republic of Korea.
Kim
Kyoung-Mee
KM
Kim
Jae J
JJ
Lee
Jun-Haeng
JH
Rhee
Jong-Chul
JC
Ko
Young-Hyeh
YH
D000328:Adult; D000368:Aged; D002135:Calcium-Binding Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D019942:Genes, p16; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000473:pathology; D064246:Mad2 Proteins; D008297:Male; D008875:Middle Aged; D012097:Repressor Proteins / Q000235:genetics*
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D012097:Repressor Proteins