Analysis of mutations of ras and p53 gene in multiple myeloma.
- Author:
Jeong Hee KIM
1
;
Young Il KIM
;
Si Young KIM
;
Hwi Joong YOON
;
Kyung Sam CHO
Author Information
1. Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Multiple myeloma;
N-ras;
K-ras;
p53;
Mutation;
PCR-SSCP;
Direct sequencing
- MeSH:
Bone Marrow;
DNA;
Exons;
Genes, p53*;
Genes, ras;
Genes, Tumor Suppressor;
Humans;
Male;
Middle Aged;
Multiple Myeloma*;
Oncogenes;
Plasma Cells;
Polymerase Chain Reaction;
Tics
- From:Korean Journal of Medicine
1998;54(3):363-374
- CountryRepublic of Korea
- Language:Korean
-
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.
