INFREQUENT INVOLVEMENT OF MUTATIONS ON NEUROFIBROMATOSIS TYPE-1, H-RAS, K-RAS AND N-RAS IN UROTHELIAL TUMORS

被引:19
作者
UCHIDA, T
WADA, C
ISHIDA, H
EGAWA, S
AO, T
YOKOYAMA, E
KOSHIBA, K
机构
[1] Department of Urology and Clinical Pathology, Kitasato University School of Medicine, Kanagawa
关键词
NF1; GENE; H-RAS; K-RAS; N-RAS; UROTHELIAL TUMORS; PCR-SSCP ANALYSIS;
D O I
10.1159/000282753
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
The neurofibromatosis type 1 (NF1) gene is considered a tumor-suppressor gene whose product acts upstream of ras. The ras gene is an oncogene very commonly detected in human cancers and consists of three families, H-ras, K-ras and N-ras. These genes are converted to active oncogenes by point mutations in codon 12, 13, or 61. Examination was made of the mutations of these genes in 39 urothelial malignant tumors (31 bladder cancer, 6 renal pelvic tumor, and 2 ureter tumors) using polymerase chain reaction single-stranded conformation polymorphism and direct sequencing methods. Three of 39 (7.7%) cases showed mobility shifts in the vas family gene but no point mutations in NF1 and N-ras genes could be detected. Mutations were found in 1 case in H-ras at codon 13 (GGT-GTT/GGT) and K-ras at codon 12 in 2 cases (GGT-GCT/GGT, GGT-GTT/GGT). All 3 cases had progressed far beyond grade 2 and stage pT2. It follows from the above that NF1 and ras gene mutations are infrequent in the pathogenesis of urothelial tumors.
引用
收藏
页码:63 / 67
页数:5
相关论文
共 29 条
[1]  
Bishop J.M., Molecular themes in oncogenesis, Cell, 64, (1991)
[2]  
Barbacid M., Ras genes, Annu Rev Biochem, 56, (1987)
[3]  
Xu G., O'Connell P., Viskochil D., Cawthon R., Robertson M., Culver M., Dunn D., Stevens J., Gesteland R., White R., Weiss R., The neurofibromatosis type 1 gene encodes a protein related to GAP, Cell, 62, (1990)
[4]  
Martin G.A., Viskochil D., Bollag G., McCabe P.C., Crosier W.J., Haubruck H., Conroy L., Clark R., O'Connell P., Cawthon R.M., Innis M.A., McCormick F., The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p 21, Cell, 63, (1990)
[5]  
Li Y., Bollag G., Clark R., Stevens J., Connory L., Fults D., Ward K., Friedman E., Samowitz W., Robertson M., Bradley P., McCormick F., White R., Cawthon R., Somatic mutations in the neurofibromatosis 1 gene in human tumors, Cell, 69, (1992)
[6]  
Anderson L.B., Fountain J.W., Gutmann D.H., Tarle S.A., Glover T.W., Dracopoli N.C., Housman D.E., Collins F.S., Mutations in the NFI gene in sporadic malignant melanoma cell lines, Nature Genet, 3, (1993)
[7]  
The I., Murthy A.E., Hannigan G.E., Jacoby L.B., Menon A.G., Gusella J.F., Bernards A., NFI gene mutations in neuroblastoma, Nature Genet, 3, (1993)
[8]  
Spiessl B., Beahrs O.H., Hermanek P., Hutter R.V.P., Scheibe O., Sobin L.H., Wagner G., UICC. TNM Classification of Malignant Tumours, pp. 276-286, (1990)
[9]  
Herrmann B.G., Frishauf A.M., Isolation of genomic DNA, Guide to Molecular Cloning Technique, pp. 180-183, (1987)
[10]  
Marchuk D.A., Saulino A.M., Tavakkol R., Swaroop M., Wallace M.R., Andersen L.B., Mitchell A.L., Gutmann D.M., Boguski M., Collins F.S., cDNA cloning of the type 1 neurofibromatosis gene: Complete sequence of the NFI gene product, Genomics, 11, (1991)