Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database
Open accessAbstract
The tumor suppressor gene TP53 is frequently mutated in human cancers. More than 75% of all mutations are missense substitutions that have been extensively analyzed in various yeast and human cell assays. The International Agency for Research on Cancer (IARC) TP53 database (www-p53.iarc.fr) compiles all genetic variations that have been reported in TP53. Here, we present recent database developments that include new annotations on the functional properties of mutant proteins, and we perform a systematic analysis of the database to determine the functional properties that contribute to the occurrence of mutational "hotspots" in different cancer types and to the phenotype of tumors. This analysis showed that loss of transactivation capacity is a key factor for the selection of missense mutations, and that difference in mutation frequencies is closely related to nucleotide substitution rates along TP53 coding sequence. An interesting new finding is that in patients with an inherited missense mutation, the age at onset of tumors was related to the functional severity of the mutation, mutations with total loss of transactivation activity being associated with earlier cancer onset compared to mutations that retain partial transactivation capacity. Furthermore, 80% of the most common mutants show a capacity to exert dominant-negative effect (DNE) over wild-type p53, compared to only 45% of the less frequent mutants studied, suggesting that DNE may play a role in shaping mutation patterns. These results provide new insights into the factors that shape mutation patterns and influence mutation phenotype, which may have clinical interest.
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In KRAS-mutant NSCLC and GEMMs, TP53 co-mutations correlate with an inflamed immune microenvironment and higher PD-L1 on tumor cells.
“TP53 co-mutations are associated with an inflamed tumor immune microenvironment and increased tumor cell PD-L1 expression in KRAS-mutant NSCLC and GEMMs.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [144]
The vast majority of TP53 mutations in t-AML/t-MDS have previously been identified as pathogenic.
“the vast majority of these mutations have previously been identified as pathogenic10.”
From Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia (2015) · cites this paper as [10]
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“i1 i2 i3 i4 i5 i6 i7 i8 i9 i10 (41, 10,739) (1, 115) (2, 92) (5, 775) (2, 81) (4, 567) (7, 342) (1, 92) (13, 2,817) (5, 919) Transactivation domains Prolinerich domain DNA-binding domain Tetramerization domain”
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“12 site mutations, which generally result in no protein expression (14), have been reported as only 2% of all TP53 mutations across tumor types (27).”
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Yizhak, K., Aguet, F., Kim, J., Hess, J. M., Kübler, K., Grimsby, J., Frazer, R., Zhang, H., Haradhvala, N. J., Rosebrock, D., et al. (2019) · Science · doi:10.1126/science.aaw0726 · Cited by 500 · see citing works
“Reviewing the International Agency for Research on Cancer (IARC) TP53 database (43), we found that all of these mutations were annotated as deleterious by the SIFT algorithm (44).”
BackgroundWalsh, T., Lee, M. K., Casadei, S., Thornton, A., Stray, S. M., Pennil, C. C., Nord, A. S., Mandell, J. B., Swisher, E. M., & King, M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1007983107 · Cited by 485 · see citing works
“, p53_721G > A) (18), we also compared all variants to gene-specific mutation databases.”
ResultThe p53 network: cellular and systemic DNA damage responses in aging and Cancer
Reinhardt, H. C., & Schumacher, B. (2012) · Trends in Genetics · doi:10.1016/j.tig.2011.12.002 · Cited by 458 · see citing works
Lai, A., Kharbanda, S., Pope, W. B., Tran, A. N., Solis, O. E., Peale, F. V., Jr., Forrest, W. F., Pujara, K., Carrillo, J., Pandita, A., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.8715 · Cited by 432 · see citing works
Clinicopathological and molecular characterisation of ‘multiple‐classifier’ endometrial carcinomas
León‐Castillo, A., Vázquez, E. G., Nout, R. A., Smit, V. T. H. B. M., McAlpine, J. N., McConechy, M. K., Kommoss, S., Brucker, S. Y., Carlson, J. W., Epstein, E., et al. (2019) · The Journal of Pathology · doi:10.1002/path.5373 · Cited by 427 · see citing works
“TP53 mutations were assessed using the public databases COSMIC [20], ClinVar [21], and IARC TP53 mutations database [22], as well as the in silico”
MethodPersonalized genomic analyses for cancer mutation discovery and interpretation
Jones, S., Anagnostou, V., Lytle, K., Parpart-Li, S. T., Nesselbush, M. C., Riley, D. R. J., Shukla, M., Chesnick, B., Kadan, M., Papp, E., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa7161 · Cited by 413 · see citing works
“Each mutation was compared to published alterations using the ClinVar database (41) and locus-specific databases including the Breast Cancer Information Core (BIC) database for BRCA1 and BRCA2 (42), the Leiden Open Variation Databases (LOVD) for ATM, BRIP1, FA genes, and PALB2 (43), the International Agency for Resear…”
MethodCai, Y., Song, W., Li, J., Jing, Y., Liang, C., Zhang, L., Zhang, X., Zhang, W., Liu, B., An, Y., et al. (2022) · Science China Life Sciences · doi:10.1007/s11427-022-2161-3 · Cited by 436 · see citing works
Resveratrol: Its Biologic Targets and Functional Activity
Pervaiz, S., & Holme, A. L. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2412 · Cited by 411 · see citing works
The role of mutant p53 in human cancer
Goh, A. M., Coffill, C. R., & Lane, D. P. (2010) · The Journal of Pathology · doi:10.1002/path.2784 · Cited by 398 · see citing works
Clinical Outcomes and Correlates of TP53 Mutations and CancerPreprint
Robles, A. I., & Harris, C. C. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001016 · Cited by 394 · see citing works
“fr) using the provided bioinformatics tools (Petitjean et al. 2007).”
BackgroundTP53 Mutations in Nonsmall Cell Lung Cancer
Mogi, A., & Kuwano, H. (2011) · BioMed Research International · doi:10.1155/2011/583929 · Cited by 392 · see citing works
“In fact, TP53 mutations are the most extensively studied mutations in lung cancer, and a database of all published mutations is maintained mainly by the IARC, as noted above.”
MethodInfluentialXu-Monette, Z. Y., Wu, L., Visco, C., Tai, Y. C., Tzankov, A., Liu, W., Montes‐Moreno, S., Dybkær, K., Chiu, A., Orazi, A., et al. (2012) · Blood · doi:10.1182/blood-2012-05-433334 · Cited by 390 · see citing works
Targeted rescue of a destabilized mutant of p53 by an in silico screened drug
Boeckler, F. M., Joerger, A. C., Jaggi, G., Rutherford, T. J., Veprintsev, D. B., & Fersht, A. R. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805326105 · Cited by 389 · see citing works
The molecular pathogenesis of head and neck squamous cell carcinoma
Rothenberg, S. M., & Ellisen, L. W. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59889 · Cited by 362 · see citing works
“As in other human cancers, missense mutations primarily within the DNA binding domain account for 75% of all mutations in the TP53 gene and confer both dominant negative and poorly understood gain-of-function properties (12–15).”
The Tumor Suppressor p53: From Structures to Drug DiscoveryPreprint
Joerger, A. C., & Fersht, A. R. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a000919 · Cited by 356 · see citing works
The p53/miR-34 axis in development and disease
Rokavec, M., Li, H., Jiang, L., & Hermeking, H. (2014) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mju003 · Cited by 354 · see citing works
“TP53 mutations can be somatic or germline, where patients that inherit a mutant TP53 allele (Li–Fraumeni syndrome) develop a variety of early onset malignancies with 100% penetrance (Petitjean et al., 2007).”
BackgroundMcHale, C. M., Zhang, L., & Smith, M. T. (2011) · Carcinogenesis · doi:10.1093/carcin/bgr297 · Cited by 349 · see citing works
Squamous Cell Carcinoma of the Lung: Molecular Subtypes and Therapeutic Opportunities
Perez-Moreno, P., Brambilla, E. M., Thomas, R. K., & Soria, J. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2370 · Cited by 347 · see citing works
“sions and is compatible with the mutagenic effects of tobacco carcinogens (71).”
A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian Carcinomas
Soragni, A., Janzen, D. M., Johnson, L. M., Lindgren, A. G., Thai-Quynh Nguyen, A., Tiourin, E., Soriaga, A. B., Lu, J., Jiang, L., Faull, K. F., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2015.12.002 · Cited by 341 · see citing works
“With thousands of different p53 mutations described (IARC TP53 database, http://p53.iarc.fr) (Petitjean et al., 2007), we cannot yet anticipate which will respond to ReACp53, other than the well-established aggregation-prone mutations.”
BackgroundInfluentialClinical impact of small TP53 mutated subclones in chronic lymphocytic leukemia
Rossi, D., Khiabanian, H., Spina, V., Ciardullo, C., Bruscaggin, A., Famà, R., Rasi, S., Monti, S. M., Deambrogi, C., Paoli, L. D., et al. (2014) · Blood · doi:10.1182/blood-2013-11-539726 · Cited by 338 · see citing works
“TP53 mutations were annotated using the IARC TP53 database.(27) For each TP53 missense mutation, the CDKN1A promoter-specific transcriptional activity measured in yeast functional assays was extracted and expressed as percent of wild-type activity.”
MethodMolecular Biology of Osteosarcoma
Czarnecka, A. M., Synoradzki, K. J., Firlej, W., Bartnik, E., Sobczuk, P., Fiedorowicz, M., Grieb, P., & Rutkowski, P. L. (2020) · Cancers · doi:10.3390/cancers12082130 · Cited by 343 · see citing works
Tumor-Suppressor Functions of the TP53 PathwayPreprint
Aubrey, B. J., Strasser, A., & Kelly, G. L. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026062 · Cited by 331 · see citing works
“The importance of the Tp53 gene as a tumor suppressor is highlighted in human cancer where it is the most commonly mutated gene, with mutations found in a broad variety of cancer types (Vogelstein et al. 2000; Petitjean et al. 2007).”
BackgroundMDM4 is a key therapeutic target in cutaneous melanoma
Gembarska, A., Luciani, F., Fedele, C., Russell, E. A., Dewaele, M., Villar, S., Zwolinska, A., Haupt, S., de Lange, J., Yip, D., et al. (2012) · Nature Medicine · doi:10.1038/nm.2863 · Cited by 327 · see citing works
Allele-Specific p53 Mutant Reactivation
Yu, X., Vázquez, A., Levine, A. J., & Carpizo, D. R. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.03.042 · Cited by 320 · see citing works
“TP53 is the most frequently mutated gene in human cancer with mutation frequencies ranging from 38%–50% in some reports to as high as 75% and 96% in pancreatic adenocarcinoma and high-grade serous ovarian carcinomas, respectively (Hingorani et al., 2005; Cancer Genome Atlas Research Network, 2011; Petitjean et al., 20…”
Paleček, E., Tkáč, J., Bartošík, M., Bertók, T., Ostatná, V., & Palecek, J. J. (2015) · Chemical Reviews · doi:10.1021/cr500279h · Cited by 319 · see citing works
Singh, N., Piskorz, A., Bosse, T., Jimenez‐Liñan, M., Rous, B., Brenton, J. D., Gilks, C. B., & Köbel, M. (2019) · The Journal of Pathology · doi:10.1002/path.5375 · Cited by 319 · see citing works
“Rare SNVs with potential tolerated or benign predictions were further characterised using the IARC (WHO) TP53 mutation database [27] (supplementary material, Table S2).”
MethodAdvances in Chemical Carcinogenesis: A Historical Review and Prospective
Loeb, L. A., & Harris, C. C. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-2852 · Cited by 314 · see citing works
Rossi, D., Cerri, M., Deambrogi, C., Sozzi, E., Cresta, S., Rasi, S., Paoli, L. D., Spina, V., Gattei, V., Capello, D., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-1630 · Cited by 309 · see citing works
Molecular biomarkers in acute myeloid leukemia
Prada‐Arismendy, J., Arroyave-Ospina, J. C., & Röthlisberger, S. (2016) · Blood Reviews · doi:10.1016/j.blre.2016.08.005 · Cited by 303 · see citing works
The combined status of ATM and p53 link tumor development with therapeutic responsePreprint
Jiang, H., Reinhardt, H. C., Bártková, J., Tommiska, J., BLOMQVIST, C. P., Nevanlinna, H. A., Bártek, J., Yaffe, M. B., & Hemann, M. T. (2009) · Genes & Development · doi:10.1101/gad.1815309 · Cited by 303 · see citing works
“6; Petitjean et al. 2007)—a number consistent with the 29% seen in human cancers examined in this study.”
BackgroundResultRuijs, M., Verhoef, S., Rookus, M. A., Pruntel, R., van der Hout, A. H., Hogervorst, F. B. L., Kluijt, I., Sijmons, R. H., Aalfs, C. M., Wagner, A., et al. (2010) · Journal of Medical Genetics · doi:10.1136/jmg.2009.073429 · Cited by 304 · see citing works
TP53 Mutation Spectrum in Breast Cancer Is Subtype Specific and Has Distinct Prognostic Relevance
Silwal‐Pandit, L., Vollan, H. K. M., Chin, S., Rueda, O. M., McKinney, S., Osako, T., Quigley, D. A., Kristensen, V. N., Aparicio, S. A. J. R., Børresen‐Dale, A., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2943 · Cited by 304 · see citing works
“Mutational hotspots (5) were observed in codons 175, 179, 196, 213, 245, 248, 273, 278, 285, and 306.”
BackgroundThe rebel angel: mutant p53 as the driving oncogene in breast cancer
Walerych, D., Napoli, M., Collavin, L., & Sal, G. D. (2012) · Carcinogenesis · doi:10.1093/carcin/bgs232 · Cited by 287 · see citing works
“mutations [4].”
Regulation of the p53 response and its relationship to cancer
Meek, D. W. (2015) · Biochemical Journal · doi:10.1042/bj20150517 · Cited by 291 · see citing works
Pathological Unfoldomics of Uncontrolled Chaos: Intrinsically Disordered Proteins and Human Diseases
Uversky, V. N., Davé, V., Iakoucheva, L. M., Malaney, P., Metallo, S. J., Pathak, R. R., & Joerger, A. C. (2014) · Chemical Reviews · doi:10.1021/cr400713r · Cited by 288 · see citing works
Two hot spot mutant p53 mouse models display differential gain of function in tumorigenesis
Hanel, W. G., Marchenko, N. D., Xu, S., Yu, S., Weng, W., & Moll, U. M. (2013) · Cell Death and Differentiation · doi:10.1038/cdd.2013.17 · Cited by 278 · see citing works
“For the human analysis, we used the latest p53 IARC database (version R15) that contains extensive clinical information regarding tumor onset in carriers of p53 germline mutations.(19) All Li–Fraumeni patients with large deletions, nonsense, splicing and frameshift mutations were considered ‘null/þ ’ in this analysis.”
MethodLi-Fraumeni syndrome: cancer risk assessment and clinical management
McBride, K. A., Ballinger, M. L., Killick, E., Kirk, J., Tattersall, M. H. N., Eeles, R. A., Thomas, D. M., & Mitchell, G. (2014) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2014.41 · Cited by 279 · see citing works
Zhao, M., Sano, D., Pickering, C. R., Jasser, S. A., Henderson, Y. C., Clayman, G. L., Sturgis, E. M., Ow, T. J., Lotan, R., Carey, T. E., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-0690 · Cited by 277 · see citing works
“Another important driver of HNSCC is TP53 mutation (33, 34).”
BackgroundCastéra, L., Krieger, S., Rousselin, A., Legros, A., Baumann, J., Bruet, O., Brault, B., Fouillet, R., Goardon, N., Letac, O., et al. (2014) · European Journal of Human Genetics · doi:10.1038/ejhg.2014.16 · Cited by 266 · see citing works
An integer linear programming approach for finding deregulated subgraphs in regulatory networks
Backes, C., Rurainski, A., Klau, G. W., Müller, O. J., Stöckel, D., Gerasch, A., Küntzer, J., Maisel, D., Ludwig, N., Hein, M., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr1227 · Cited by 259 · see citing works
“In addition, it is known that HT-29 carries TP53 mutations, whereas HCT-116 is TP53 wildtype [see IARC TP53 DB (52), Roche Cancer Genome Database (53)].”
Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma
D’souza, S., Lau, K. C. K., Coffin, C. S., & Patel, T. R. (2020) · World Journal of Gastroenterology · doi:10.3748/wjg.v26.i38.5759 · Cited by 272 · see citing works
Mirabello, L., Zhu, B., Koster, R., Karlins, E., Dean, M., Yeager, M., Gianferante, M., Spector, L. G., Morton, L. M., Karyadi, D., et al. (2020) · JAMA Oncology · doi:10.1001/jamaoncol.2020.0197 · Cited by 243 · see citing works
Phase I Study of a Systemically Delivered p53 Nanoparticle in Advanced Solid Tumors
Senzer, N. N., Nemunaitis, J. J., Nemunaitis, D., Bedell, C., Edelman, G. M., Barve, M. A., Nunan, R., Pirollo, K. F., Rait, A. S., & Chang, E. H. (2013) · Molecular Therapy · doi:10.1038/mt.2013.32 · Cited by 250 · see citing works
p53 and its isoforms in cancer
Bourdon, J. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6603886 · Cited by 245 · see citing works
“The changes upon stimuli of the balance and interactions between the isoforms are likely to be fundamental to our understanding in the transition between normal cell cycling and the onset of tumour formation.”
BackgroundInfluentialHalogen-Enriched Fragment Libraries as Leads for Drug Rescue of Mutant p53
Wilcken, R., Liu, X., Zimmermann, M. O., Rutherford, T. J., Fersht, A. R., Joerger, A. C., & Boeckler, F. M. (2012) · Journal of the American Chemical Society · doi:10.1021/ja301056a · Cited by 243 · see citing works
Stengel, A., Kern, W., Haferlach, T., Meggendorfer, M., Fasan, A., & Haferlach, C. (2016) · Leukemia · doi:10.1038/leu.2016.263 · Cited by 244 · see citing works
Obesity, DNA Damage, and Development of Obesity-Related Diseases
Włodarczyk, M., & Nowicka, G. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20051146 · Cited by 246 · see citing works
“A higher mutation amount in the p53 gene was found in cancers [97].”
BackgroundTP53 loss creates therapeutic vulnerability in colorectal cancer
Liu, Y., Zhang, X., Han, C., Wan, G., Huang, X., Ivan, C., Jiang, D., Rodriguez‐Aguayo, C., Lopez‐Berestein, G., Rao, P. H., et al. (2015) · Nature · doi:10.1038/nature14418 · Cited by 240 · see citing works
Marcel, V., Tran, P. L. T., Sagne, C., Martel‐Planche, G., Vaslin, L., Teulade‐Fichou, M., Hall, J. A., Mergny, J., Hainaut, P. L., & Dyck, E. V. (2010) · Carcinogenesis · doi:10.1093/carcin/bgq253 · Cited by 241 · see citing works
Self-citationSarcomas in TP53 germline mutation carriers
Ognjanovic, S., Olivier, M., Bergemann, T. L., & Hainaut, P. L. (2011) · Cancer · doi:10.1002/cncr.26390 · Cited by 236 · see citing works
“html [last accessed October 2010]) was used.(19) This data set was compiled from information on TP53 germline mutation carriers and on families with LFS and related syndromes affected by cancer published in peerreviewed articles between 1990 and 2009.”
MethodInfluentialSelf-citationSmall molecule induced reactivation of mutant p53 in cancer cells
Liu, X., Wilcken, R., Joerger, A. C., Chuckowree, I., Amin, J., Spencer, J., & Fersht, A. R. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt305 · Cited by 235 · see citing works
“Analysis of the p53 mutation database of the International Agency for Research on Cancer (7) suggests that about 30–40% of p53 cancer mutations are structural mutations (8).”
BackgroundHereditary Ovarian Cancer: Not Only BRCA 1 and 2 Genes
Toss, A., Tomasello, C., Razzaboni, E., Contu, G., Grandi, G., Cagnacci, A., Schilder, R., & Cortesi, L. (2015) · BioMed Research International · doi:10.1155/2015/341723 · Cited by 240 · see citing works
Targeting the nucleolus for cancer intervention
Quin, J. E., Devlin, J. R., Cameron, D. P., Hannan, K. M., Pearson, R. B., & Hannan, R. D. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.12.009 · Cited by 224 · see citing works
“Correspondingly, p53 is mutated in approximately half of all human tumors [84], and in the”
BackgroundWasserman, J. D., Novokmet, A., Eichler-Jonsson, C., Ribeiro, R. C., Galindo, C. R., Zambetti, G. P., & Malkin, D. M. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2013.52.6863 · Cited by 229 · see citing works
“This series was enriched for two alleles, P152L (n 5) and R158H (n 3), a finding that is not replicated when examining the overall distribution of TP53 alleles in patients with ACC.12 Both series reported small numbers of children from geographically limited catchments.”
BackgroundInfluentialComparison of predicted and actual consequences of missense mutations
Miosge, L. A., Field, M. A., Sontani, Y., Cho, V., Johnson, S., Palkova, A., Balakishnan, B., Liang, R., Zhang, Y., Lyon, S., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1511585112 · Cited by 222 · see citing works
“Instead this individual displayed a syndrome of familial adenomatous polyposis (FAP) that was at the severe end of the spectrum and carried an additional germ-line mutation in the APC tumor suppressor gene that is typically inactivated in FAP (40).”
BackgroundMethodResultInfluentialLechner, M., Frampton, G. M., Fenton, T. R., Feber, A., Palmer, G. A., Jay, A., Pillay, N., Forster, M. D., Cronin, M. T., Lipson, D., et al. (2013) · Genome Medicine · doi:10.1186/gm453 · Cited by 219 · see citing works
“However, this mutation (R290C, Additional File 1, Table S2) causes only a 40% decrease in TP53 function and has been detected in sarcomas harboring MDM2 amplification [24, 25].”
BackgroundControl of metabolism by p53 – Cancer and beyond
Labuschagne, C. F., Zani, F., & Vousden, K. H. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.06.001 · Cited by 219 · see citing works
“While alterations in the p53 gene occur in well over half of all cancers, many of these are subtle missense mutations, giving rise to the expression of a p53 protein altered at only a single amino acid residue [95].”
Backgroundp53 in breast cancer subtypes and new insights into response to chemotherapy
Bertheau, P., Lehmann‐Che, J., Varna, M., Dumay, A., Poirot, B., Porcher, R., Turpin, E., Plassa, L., de Roquancourt, A., Bourstyn, E., et al. (2013) · The Breast · doi:10.1016/j.breast.2013.07.005 · Cited by 216 · see citing works
Biological functions of p53 isoforms through evolution: lessons from animal and cellular models
Marcel, V., Dichtel-Danjoy, M.-L., Sagne, C., Hafsi, H., Ma, D., Ortiz‐Cuaran, S., Olivier, M., Hall, J. A., Mollereau, B., Hainaut, P. L., et al. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.120 · Cited by 210 · see citing works
Self-citationHof, J., Groeneveld‐Krentz, S., van Schewick, C., Körner, G., Shalapour, S., Rhein, P., Karawajew, L., Ludwig, W., Seeger, K., Henze, G., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.34.8144 · Cited by 209 · see citing works
Choudhury, A., Nelson, L. D., Teo, M. T. W., Chilka, S., Bhattarai, S., Johnston, C. F., Elliott, F., Lowery, J., Taylor, C., Churchman, M., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1202 · Cited by 208 · see citing works
- Authors
- Petitjean, A., Mathe, E., Kato, S., Ishioka, C., Tavtigian, S. V., Hainaut, P., & Olivier, M.
- Affiliations
- Centre international de recherche sur le cancer (FR)
- Tohoku University (JP)
- World Health Organization (CH)
- Corresponding author
- Hainaut, Pierre
- ORCID
- Venue
- Human Mutation
- Publisher
- Wiley
- Published
- 2007-06
- Volume
- 28
- Issue
- 6
- Pages
- 622-629
- ISSN
- 1059-7794 (ISSN-L)
- 1098-1004
- OpenAlex
- W1986076152
- Cited by
- 1,598
- References
- 26
- Citations by year
- 2026: 24 · 2025: 36 · 2024: 34 · 2023: 42 · 2022: 59 · 2021: 87 · 2020: 68 · 2019: 81 · 2018: 75 · 2017: 83 · 2016: 120 · 2015: 135 · 2014: 136 · 2013: 131 · 2012: 143
- FWCI
- 41.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 3014 d)
- Locations
- Human Mutation (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Environmental Health Sciences
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- TP53, TP53 mutation, missense mutations, mutational hotspots, dominant negative effect, tumor suppressor, nucleotide substitution rates, mutation patterns, tumor phenotype
- MeSH terms
- DNA Mutational Analysis, Humans, Mutation, Neoplasms, Phenotype, Transcriptional Activation, Tumor Suppressor Protein p53, Age of Onset, Germ-Line Mutation, Databases, Genetic
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