Mutations in the p53 gene occur in diverse human tumour types
Janice M. Nigro,Suzanne J. Baker,Antonette C. Preisinger,J M Jessup,R. Hostetter,Karen R. Cleary,S H Bigner,Nancy E. Davidson,Stephen B. Baylin,Peter Devilee +9 more
TLDR
It is suggested that most tumours with allelic deletions of chromosome 17p contain p53 point mutations resulting in amino-acid substitutions, and p53 gene mutations are clustered in four 'hot-spots' which exactly coincide with the four most highly conserved regions of the gene.Abstract:
The p53 gene has been a constant source of fascination since its discovery nearly a decade ago. Originally considered to be an oncogene, several convergent lines of research have indicated that the wild-type gene product actually functions as a tumour suppressor gene. For example, expression of the neoplastic phenotype is inhibited, rather than promoted, when rat cells are transfected with the murine wild-type p53 gene together with mutant p53 genes and/or other oncogenes. Moreover, in human tumours, the short arm of chromosome 17 is often deleted. In colorectal cancers, the smallest common region of deletion is centred at 17p13.1; this region harbours the p53 gene, and in two tumours examined in detail, the remaining (non-deleted) p53 alleles were found to contain mutations. This result was provocative because allelic deletion coupled with mutation of the remaining allele is a theoretical hallmark of tumour-suppressor genes. In the present report, we have attempted to determine the generality of this observation; that is, whether tumours with allelic deletions of chromosome 17p contain mutant p53 genes in the allele that is retained. Our results suggest that (1) most tumours with such allelic deletions contain p53 point mutations resulting in amino-acid substitutions, (2) such mutations are not confined to tumours with allelic deletion, but also occur in at least some tumours that have retained both parental 17p alleles, and (3) p53 gene mutations are clustered in four 'hot-spots' which exactly coincide with the four most highly conserved regions of the gene. These results suggest that p53 mutations play a role in the development of many common human malignancies.read more
Citations
More filters
Journal ArticleDOI
A genetic model for colorectal tumorigenesis
Eric R. Fearon,Bert Vogelstein +1 more
TL;DR: A model for the genetic basis of colorectal neoplasia that includes the following salient features is presented, which may be applicable to other common epithelial neoplasms, in which tumors of varying stage are more difficult to study.
Journal ArticleDOI
p53 mutations in human cancers
TL;DR: The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues as mentioned in this paper.
Journal ArticleDOI
Cancer Cell Cycles
TL;DR: Genetic alterations affecting p16INK4a and cyclin D1, proteins that govern phosphorylation of the retinoblastoma protein and control exit from the G1 phase of the cell cycle, are so frequent in human cancers that inactivation of this pathway may well be necessary for tumor development.
Journal ArticleDOI
An Integrated Genomic Analysis of Human Glioblastoma Multiforme
D. Williams Parsons,Siân Jones,Xiaosong Zhang,Jimmy Lin,Rebecca J. Leary,Philipp Angenendt,Parminder Mankoo,Hannah Carter,I-Mei Siu,Gary L. Gallia,Alessandro Olivi,Roger E. McLendon,B.K. Ahmed Rasheed,Stephen T. Keir,Tatiana Nikolskaya,Yuri Nikolsky,Dana A. Busam,Hanna Tekleab,Luis A. Diaz,James Hartigan,Doug R. Smith,Robert L. Strausberg,Suely Kazue Nagahashi Marie,Sueli Mieko Oba Shinjo,Hai Yan,Gregory J. Riggins,Darell D. Bigner,Rachel Karchin,Nick Papadopoulos,Giovanni Parmigiani,Bert Vogelstein,Victor E. Velculescu,Kenneth W. Kinzler +32 more
TL;DR: Recurrent mutations in the active site of isocitrate dehydrogenase 1 (IDH1) occurred in a large fraction of young patients and in most patients with secondary GBMs and were associated with an increase in overall survival.
Journal ArticleDOI
IDH1 and IDH2 Mutations in Gliomas
Hai Yan,D. Williams Parsons,Genglin Jin,Roger E. McLendon,B.K. Ahmed Rasheed,Weishi Yuan,Ivan Kos,Ines Batinic-Haberle,Siân Jones,Gregory J. Riggins,Henry S. Friedman,Allan H. Friedman,David A. Reardon,James E. Herndon,Kenneth W. Kinzler,Victor E. Velculescu,Bert Vogelstein,Darell D. Bigner +17 more
TL;DR: Mutations of NADP(+)-dependent isocitrate dehydrogenases encoded by IDH1 and IDH2 occur in a majority of several types of malignant gliomas.
References
More filters
Journal ArticleDOI
Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase
Randall Keichi Saiki,David H. Gelfand,Susanne Stoffel,Stephen J. Scharf,Russell Higuchi,Glenn Thomas Horn,Kary B. Mullis,Henry A. Erlich +7 more
TL;DR: A thermostable DNA polymerase was used in an in vitro DNA amplification procedure, the polymerase chain reaction, which significantly improves the specificity, yield, sensitivity, and length of products that can be amplified.
Journal ArticleDOI
T Antigen Is Bound to a Host Protein in Sv40-Transformed Cells
TL;DR: It is reported here that the T antigen in a line of SV40-transformed mouse cells forms an oligomeric complex with a specific cell coded protein.
Journal ArticleDOI
Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas
Suzanne J. Baker,Eric R. Fearon,Janice M. Nigro,Stanley R. Hamilton,Ann C. Preisinger,J. Milburn Jessup,P vanTuinen,David H. Ledbetter,David F. Barker,Yusuke Nakamura,Ray White,Bert Vogelstein +11 more
TL;DR: The data suggest that p53 gene mutations may be involved in colorectal neoplasia, perhaps through inactivation of a tumor suppressor function of the wild-type p53 genes.
Journal ArticleDOI
The p53 proto-oncogene can act as a suppressor of transformation
TL;DR: DNA clones of the wild-type p53 proto-oncogene inhibit the ability of E1Aplus ras or mutant p53 plus ras-activated oncogenes to transform primary rat embryo fibroblasts, suggesting that the p53 prototype can act negatively to block transformation.
Journal ArticleDOI
Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells.
TL;DR: It is concluded that SV40 infection or transformation of mouse cells stimulates the synthesis or enhances the stability of a 54K protein, which appears to be associated with SV40 T antigen in SV40-infected and -transformed cells, and is co-immunoprecipitated by hybridomas sera to SV40 large T antigen.