Aberrant gene methylation implicated in the progression of monoclonal gammopathy of undetermined significance to multiple myeloma.
Malignant transformation is a multistep process that may involve dysregulation of oncogenes and tumour suppressor genes, and monoclonal gammopathy of undetermined significance (MGUS) is believed to be a precursor of multiple myeloma. To investigate whether aberrant promoter methylation might be involved in the evolution of MGUS to multiple myeloma, we examined the p16, protein tyrosine phosphatase, non-receptor type 6 (SHP1), death-associated protein (DAP) kinase, E-cadherin and oestrogen receptor genes, most being tumour suppressor genes, by methylation-specific polymerase chain reaction. In 32 cases of multiple myeloma and 19 cases of MGUS, significantly more frequent methylation of p16 (p = 0.001), SHP1 (p< or =0.001) and E-cadherin (p< or =0.001) genes was found in multiple myeloma than in MGUS. Methylation of DAP kinase and oestrogen receptor genes was comparable in multiple myeloma and MGUS. In conclusion, methylation of p16, SHP1 and E-cadherin genes might be involved in the progression of MGUS to multiple myeloma.
Chim
Chor-Sang
CS
University Department of Medicine, Queen Mary Hospital, Hong Kong. jcschim@hku.hk
Liang
Raymond
R
Leung
Man-Hin
MH
Kwong
Yok-Lam
YL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D010265:Paraproteinemias / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic / Q000235:genetics
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins