SHORT REPORT

Aberrant gene methylation implicated in the progression of monoclonal gammopathy of undetermined significance to multiple myeloma

Chor-Sang Chim, Raymond Liang, Man-Hin Leung and Yok-Lam Kwong

University Department of Medicine, Queen Mary Hospital, Hong Kong

Correspondence to:
Correspondence to:
Dr C-S Chim
Department of Medicine, Queen Mary Hospital, Pokfulam Road, Hong Kong 852, Hong Kong; jcschim{at}hku.hk

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 (p0.001) and E-cadherin (p0.001) 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.

Abbreviations: DAP, death-associated protein; MGUS, monoclonal gammopathy of undetermined significance; MSP, methylation-specific polymerase chain reaction; SHP1, protein tyrosine phosphatase, non-receptor type 6.

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• Chim, C.-S., Liang, R., Fung, T.-K., Choi, C.-L., Kwong, Y.-L. (2007). Epigenetic dysregulation of the death-associated protein kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in multiple myeloma. J. Clin. Pathol. 60: 664-669 [Abstract] [Full Text]