Mutational analysis of N-ras, p53, p16INK4a, p14ARF and CDK4 genes in primary human malignant mesotheliomas.
Nineteen specimens from primary human malignant mesotheliomas obtained from 19 patients were screened for activating point mutations in the oncogenes N-ras and CDK4 by combined RFLP-PCR/SSCP analysis. In addition, all tumours were screened for deletions and point mutations in the tumour suppressor genes p53, p16INK4a (CDKN2A) and p14ARF (exon-1beta) by combined multiplex-PCR/SSCP analysis. No mutations were found in N-ras, p53 and CDK4. Three tumours displayed homozygous deletion (co-deletion of exons 1, 2 and 3) of p16INK4a. One of them displayed additional homozygous deletion of p14ARF (exon-1beta). Two silent point mutations and 2 polymorphisms were found in p16INK4a in 3 tumours. Our preliminary data indicate that disarrangement of the Rb1 pathway may be involved in mesothelioma formation.
Papp
T
T
Department of Biological Sciences, Institute for Cell Biology and Biosystems Technology, University of Rostock, Universitätsplatz 2, 18051 Rostock, Germany. thilo.papp@biologie.uni-rostock.de
Schipper
H
H
Pemsel
H
H
Bastrop
R
R
Muller
K M
KM
Wiethege
T
T
Weiss
D G
DG
Dopp
E
E
Schiffmann
D
D
Rahman
Q
Q
D000328:Adult; D000368:Aged; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D019942:Genes, p16 / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018301:Neoplasms, Mesothelial / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D014407:Tumor Cells, Cultured / Q000502:physiology; D025803:Tumor Suppressor Protein p14ARF
D011506:Proteins; D011518:Proto-Oncogene Proteins; D025803:Tumor Suppressor Protein p14ARF; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases