Analysis of mutations of ras and p53 gene in multiple myeloma

Kim, Jeong Hee; Kim, Young Il; Kim, Si Young; Yoon, Hwi Joong; Cho, Kyung Sam

Abstract

BACKGROUND: Multiple myeloma is a malignant prolif eration of plasma cells producing monoclonal immunog lobulins. The pathogenesis of this disease is still unkno wn. Karyotypic complexity and stepwise disease progre ssion in multiple myeloma suggest that the development of multiple myeloma is a multistep process in genetic events, such as oncogene activation or tumor suppressor gene inactivation. Alterations of ras oncogene or p53 tumor sup pressor gene are involved in various type of human cancers. The aim of this study was to determine the frequency of ras and p53 gene mutations in multiple myeloma, and to analyze its association with clinical parameter and clinical outcome.
METHODS
Mutations of N-, K-ras exon 1 & 2 and p53 exon 5-8 were observed in 33 patients with multiple myeloma. Genomic DNA was isolated from mononuclear cells separated from bone marrow samples. Extracted DNAs were screened for mutations by single-strand con formation polymorphism analysis of PCR products (PCR SSCP). DNA fragments displaying an altered electrophore tic mobility were further studied by direct sequencing to confirm and characterize the nature of the mutations.
RESULTS
No mutation was found at N-, K-ras exon 1, K-ras exon 2 or p53 exon 5-8. Only one patient has N-ras exon 2 mutation(1/33 patients, 3%). By direct sequencing of PCR products, I confirmed and detected a CAA-->AAA transversion(glutamine-->lysine). The patient was a 61-year-old male in progressive state. M protein was IgG/kappa type. Bone marrow aspirate revealed a 67% plasma cell infiltration.
CONCLUSION
Although the number of patients is small, these data revealed low frequency of N-ras, K-ras and p53 gene mutation in multiple myeloma. Ras and p53 gene mutations may have limited role in pathogenesis of mulitple myeloma and may associate with tumor progres sion rather than initiation.