Methylation of promoter region in p27 gene plays a role in the development of lymphoid malignancies.
p27 belong to the cyclin-dependent kinase inhibitor family and plays an important role in regulation of cell cycle progression. Expression of these genes is epigenetically suppressed by methylation of their promoter regions. In this study, we examined protein expression and methylation status of the promoter region of p27 in 70 cases with non-Hodgkin's lymphoma and their relationship with proliferative activity of the tumor cells as revealed by Ki-67 index. There were 35 cases of B-cell, 11 of T-cell, 23 of NK/T-cell lymphoma, and 1 undetermined type. Immunohistochemically the loss of p27 protein expression was observed in 24 (69%) of 35 cases. Significant inverse correlation between p27 protein expression and Ki-67 index was found. Single strand conformation polymorphism (SSCP) followed by sequencing could not detect point mutations in any of the 68 cases. Bisulfite sequencing analysis showed that methylation of the promoter region of p27 were observed in 17 (25%) of 68 cases, in that several specific CpG sites around the start codon of p27 gene were preferentially methylated. Eight of 22 cases with loss of p27 protein expression showed methylation in CpG island of 5' region of p27 gene. These findings suggested that gene methylation plays a role in loss of expression of p27, which gives the cells proliferative advantages.
Nakatsuka
Shin-Ichi
S
Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Liu
Angen
A
Yao
Masayuki
M
Takakuwa
Tetsuya
T
Tomita
Yasuhiko
Y
Hoshida
Yoshihiko
Y
Nishiu
Mieko
M
Aozasa
Katsuyuki
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002648:Child; D018899:CpG Islands; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007223:Infant; D019394:Ki-67 Antigen / Q000032:analysis; D016393:Lymphoma, B-Cell / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*
D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27