The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
p53 gene mutation and ink4a-arf deletion appear to be two mutually exclusive events in human glioblastoma
Abstract
P16 and P14ARF are two tumor suppressors encoded by the locus ink4a-arf which is frequently deleted in human tumors. Recent experiments performed with mouse embryonic fibroblasts have shown that P14ARF is an upstream regulator of the P53 pathway. This raises the question as to whether in human tumors the loss of p14arf and mutation of p53 are mutually exclusive events which segregate with genetic alterations at other loci. To examine this question we performed a multigenic analysis on 29 gliomas. We analysed p53 and p14arf in relation with five other genetic loci encoding the most frequently mutated genes in human gliomas: cdkn2a, mdm2, egfr, pten and the chromosomal regions 10q23.3 and 10q25-26. Our study shows for the first time that p53 mutations and p14arf deletions appear mutually exclusive in human glioblastoma, suggesting that they may be functionally redundant in glioma tumorigenesis. The P53 pathway is, therefore, disrupted in 81.8% of malignant gliomas (WHO grades III and IV), either by mutation of the p53 gene (31.8%) or by p14arf deletion (54.5%). These tumors further showed MDM2 overexpression (9.1%), egfr oncogene amplification/egfr overexpression (50%), pten mutations (27.3%) and loss of heterozygosity (LOH) at the chromosomal regions 10q23.3 (86.4%) and 10q25-26 (100%). These alterations did not segregate with p53 mutations or p14arf deletions, while p14arf and cdkn2a were always deleted.
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“CDKN2A/ARF and TP53 are rarely co-deregulated, suggesting redundancy in the effects of their loss on GBM malignancy [39,40].”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [39]
Citations
Cites
Tumor Suppression at the Mouse INK4a Locus Mediated by the Alternative Reading Frame Product p19
Kamijo, T., Zindy, F., Roussel, M. F., Quelle, D. E., Downing, J. R., Ashmun, R. A., Grosveld, G., & Sherr, C. J. (1997) · Cell · doi:10.1016/s0092-8674(00)80452-3 · Cited by 1,566
Pomerantz, J., Schreiber-Agus, N., Liégeois, N. J., Silverman, A., Alland, L., Chin, L., Potes, J., Chen, K., Orlow, I., Lee, H.-W., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81400-2 · Cited by 1,521
Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53
Oliner, J. D., Pietenpol, J. A., Thiagalingam, S., Gyuris, J., Kinzler, K. W., & Vogelstein, B. (1993) · Nature · doi:10.1038/362857a0 · Cited by 1,474
Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization
Zindy, F., Eischen, C. M., Randle, D. H., Kamijo, T., Cleveland, J. L., Sherr, C. J., & Roussel, M. F. (1998) · Genes & Development · doi:10.1101/gad.12.15.2424 · Cited by 1,245
A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity.
Nishikawa, R., Ji, X.-D., Harmon, R. C., Lazar, C. S., Gill, G. N., Cavenee, W. K., & Huang, H. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.16.7727 · Cited by 936
Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus
Kamb, A., Shattuck-Eidens, D. M., Eeles, R. A., Liu, Q., Gruis, N. A., Ding, W., Hussey, C. E., Tran, T., Miki, Y., Weaver-Feldhaus, J., et al. (1994) · Nature Genetics · doi:10.1038/ng0994-22 · Cited by 855
Association of p19ARF with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53
Honda, R., & Yasuda, H. (1999) · The EMBO Journal · doi:10.1093/emboj/18.1.22 · Cited by 724
Frequency of homozygous deletion at p16/CDKN2 in primary human tumours
Cairns, P., Polascik, T. J., Eby, Y. J., Tokino, K., Califano, J. A., Merlo, A. U., Mao, L., Herath, J. F., Jenkins, R. B., Westra, W. H., et al. (1995) · Nature Genetics · doi:10.1038/ng1095-210 · Cited by 626
Self-citationE1A signaling to p53 involves the p19ARFtumor suppressorPreprint
de Stanchina, E., McCurrach, M. E., Zindy, F., Shieh, S.-Y., Ferbeyre, G., Samuelson, A. V., Prives, C. L., Roussel, M. F., Sherr, C. J., & Lowe, S. W. (1998) · Genes & Development · doi:10.1101/gad.12.15.2434 · Cited by 611
Interaction between the retinoblastoma protein and the oncoprotein MDM2
Xiao, Z.-X., Chen, J., Levine, A. J., Modjtahedi, N., Xing, J. W., Sellers, W. R., & Livingston, D. M. (1995) · Nature · doi:10.1038/375694a0 · Cited by 586
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The p53 Pathway in Glioblastoma
Zhang, Y., Dube, C., Gibert, M., Cruickshanks, N., Wang, B., Coughlan, M., Yang, Y., Setiady, I., Deveau, C., Saoud, K., et al. (2018) · Cancers · doi:10.3390/cancers10090297 · Cited by 440
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Recent Advances in the Treatment of Malignant Astrocytoma
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Metadata
- Authors
- Fulci, G., Labuhn, M., Maier, D., Lachat, Y., Hausmann, O., Hegi, M. E., Janzer, R. C., Merlo, A., & Van Meir, E. G.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- University Hospital of Basel (CH)
- Venue
- Oncogene
- Published
- 2000-07-28
- Volume
- 19
- Issue
- 33
- Pages
- 3816-3822
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2069294039
- Cited by
- 146
- References
- 41
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 7 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 4 · 2012: 7
- FWCI
- 7.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- glioblastoma, TP53 mutation, INK4a/ARF locus, tumor suppressor, MDM2 overexpression, EGFR amplification, PTEN mutation, CDKN2A, loss of heterozygosity, p53 pathway
- MeSH terms
- Animals, Carrier Proteins, Glioblastoma, Humans, Nuclear Proteins, Phosphoric Monoester Hydrolases, Proteins, Proto-Oncogene Proteins, Genes, Tumor Suppressor, Tumor Suppressor Protein p53, Mutagenesis, Gene Deletion, Cyclin-Dependent Kinase Inhibitor p16, Tumor Suppressor Proteins, Tumor Suppressor Protein p14ARF, PTEN Phosphohydrolase, Mice, Proto-Oncogene Proteins c-mdm2, ErbB Receptors
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