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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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“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]
In the citing paper
“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]
Citations
Cites
Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607 · cited 1×
“The tumor suppressor gene TP53 (OMIM ]191117) encodes a transcription factor that responds to several forms of cellular stress and exerts multiple, antiproliferative functions [Vogelstein et al., 2000].”
BackgroundGerm Line p53 Mutations in a Familial Syndrome of Breast Cancer, Sarcomas, and Other Neoplasms
Malkin, D., Li, F. P., Strong, L. C., Fraumeni, J. F., Nelson, C. E., Kim, D. H., Kassel, J., Gryka, M. A., Bischoff, F. Z., Tainsky, M. A., et al. (1990) · Science · doi:10.1126/science.1978757 · Cited by 3,765 · cited 1×
“Inherited TP53 mutations predispose to a wide spectrum of early-onset cancers and are associated with Li-Fraumeni and Li-Fraumeni-like syndrome (LFS and LFL, respectively) [Malkin et al., 1990].”
BackgroundPreferential Formation of Benzo[ a ]pyrene Adducts at Lung Cancer Mutational Hotspots in P53
Denissenko, M. F., Pao, A., Tang, M.-S., & Pfeifer, G. P. (1996) · Science · doi:10.1126/science.274.5286.430 · Cited by 1,650 · cited 1×
“In lung cancers, V157F, R158L, R248L, and R273L hotspots are due to G4T transversions that have been shown to be caused by the presence of benzo(a)-pyrene diol epoxide (BPDE) adducts on guanines at these codons [Denissenko et al., 1996].”
BackgroundMutant p53 gain of function in two mouse models of Li-Fraumeni syndrome
Olive, K. P., Tuveson, D. A., Ruhe, Z. C., Yin, B., Willis, N. A., Bronson, R. T., Crowley, D., & Jacks, T. (2004) · Cell · doi:10.1016/j.cell.2004.11.004 · Cited by 1,308 · cited 1×
“Studies in mouse models of LFS have reported evidence of GOF for R175H and R273H mutants [Lang et al., 2004; Olive et al., 2004].”
BackgroundThe IARC TP53 database: new online mutation analysis and recommendations to users
Olivier, M., Eeles, R., Hollstein, M., Khan, M. A., Harris, C. C., & Hainaut, P. (2002) · Human Mutation · doi:10.1002/humu.10081 · Cited by 1,248 · cited 1×
“It contains annotations related to the clinical and pathological characteristics of tumors, as well as the demographics and carcinogen exposure of patients [Olivier et al., 2002].”
BackgroundGain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome
Lang, G. A., Iwakuma, T., Suh, Y.-A., Liu, G., Rao, V. A., Parant, J. M., Valentin-Vega, Y. A., Terzian, T., Caldwell, L. C., Strong, L. C., et al. (2004) · Cell · doi:10.1016/j.cell.2004.11.006 · Cited by 1,069 · cited 1×
“Studies in mouse models of LFS have reported evidence of GOF for R175H and R273H mutants [Lang et al., 2004; Olive et al., 2004].”
Backgroundp53 and Human Cancer: The First Ten Thousand Mutations
Hainaut, P. L., & Hollstein, M. C. (1999) · Advances in cancer research · doi:10.1016/s0065-230x(08)60785-x · Cited by 999 · cited 1×
“Somatic TP53 gene alterations are frequent in most human cancers [Hainaut and Hollstein, 2000], ranging from 5 to 80% depending on the type, stage, and etiology of tumors.”
BackgroundSelf-citationKato, S., Han, S., Liu, W., Otsuka, K., Shibata, H., Kanamaru, R., & Ishioka, C. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1431692100 · Cited by 895 · cited 2×
“…2007 WILEY-LISS, INC. and a single study has performed a systematic analysis of the activity of all possible missense mutations produced by singlenucleotide substitution in the entire sequence of TP53 (2,314 mutations) on eight different p53-RE in yeast cells [Kato et al., 2003].”
BackgroundSelf-citationThe clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer.
Olivier, M., Langer√∏d, A., Carrieri, P., Bergh, J. C. S., Klaar, S., Eyfjord, J. E., Theillet, C. G., Rodríguez, C., Lidereau, R., Bièche, I., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1029 · Cited by 590 · cited 1×
“However, in a recent study on a large series of patients with breast cancer, we found that TP53 mutations were an independent factor of poor prognosis [Olivier et al., 2006], but that TA did not accurately predict differences in survival among patients with TP53 mutations.”
ResultSelf-citationOlivier, M., Goldgar, D. E., Sodha, N., Ohgaki, H., Kleihues, P., Hainaut, P. L., & Eeles, R. A. (2003) · PubMed · Cited by 480
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Items 901–999 of 999
Adduri, S., Katamoni, R., Pandilla, R., Madana, S. N., Paripati, A. K., Kotapalli, V., & Bashyam, M. D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114002 · Cited by 16
“24%) was higher than reported in the database [15].”
BackgroundResultInfluentialProtective Effect of the Y220C Mutant p53 Against Steatosis: Good News?
Gori, M., Barbaro, B., Arciello, M., Maggio, R., Viscomi, C., Longo, A., & Balsano, C. (2014) · Journal of Cellular Physiology · doi:10.1002/jcp.24550 · Cited by 16
“…is the Y220Cmissensemutation (in which a tyrosine is replaced by a cysteine) that accounts for 1.4% of somatic p53 missense mutations (cf. version R11 of the TP53 mutation database at www.p53.iarc.fr) (Petitjean et al., 2007; #Manuele Gori and Barbara Barbaro contributed equally to this work.”
BackgroundInfluentialHecht, S. S., & Hochalter, J. B. (2014) · Mutagenesis · doi:10.1093/mutage/geu024 · Cited by 16
“Mutations at these same sites have been found in lung tumours from smokers (15).”
BackgroundEvaluating Drosophila p53 as a Model System for Studying Cancer Mutations
Herzog, G., Joerger, A. C., Shmueli, M. D., Fersht, A. R., Gazit, E., & Segal, D. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.417980 · Cited by 16
“Most cancerassociated p53 mutations are found in the sequence-specific DBD of the protein, with residues Arg-175, Gly-245, Arg-248, Arg-249, Arg-273, and Arg-282 having the highest mutation frequency in human cancer (4).”
BackgroundInamura, K., Ninomiya, H., Nomura, K., Tsuchiya, E., Satoh, Y., Okumura, S., Nakagawa, K., Takata, A., Kohyama, N., & Ishikawa, Y. (2014) · Oncology Reports · doi:10.3892/or.2014.3263 · Cited by 16
Sina, M., Pedram, M., Ghojazadeh, M., Kochaki, A., & Aghbali, A. (2014) · Medicina oral, patología oral y cirugía bucal · doi:10.4317/medoral.19794 · Cited by 16
“About 90% of these mutations lead to the synthesis of a stable but nonfunctional P53 protein accumulating in the nuclei of tumor cells (16).”
BackgroundGarcia‐Canton, C., Errington, G., Anadón, A., & Meredith, C. (2014) · BMC Pharmacology and Toxicology · doi:10.1186/2050-6511-15-41 · Cited by 16
“The normal phenotype and wild-type p53 status support the use of this cell line in DNA damage studies [33-35].”
BackgroundSingle-Molecule Investigation of Response to Oxidative DNA Damage by a Y-Family DNA Polymerase
Raper, A. T., Gadkari, V. V., Maxwell, B. A., & Suo, Z. (2016) · Biochemistry · doi:10.1021/acs.biochem.6b00166 · Cited by 16
Natural (and Unnatural) Small Molecules as Pharmacological Chaperones and Inhibitors in Cancer
Betancor-Fernández, I., Timson, D. J., SALIDO, E. C., & Pey, A. L. (2017) · Handbook of experimental pharmacology · doi:10.1007/164_2017_55 · Cited by 16
Fujiwara, Y., Saito, M., Robles, A. I., Nishida, M., Takeshita, F., Watanabe, M., Ochiya, T., Yokota, J., Kohno, T., Harris, C. C., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.06.031 · Cited by 16
“TP53 is mutated and/or inactivated in half of human cancers, and dysfunction of p53 makes a critical contribution to the onset of carcinogenesis [3, 4].”
BackgroundPunganuru, S. R., Madala, H. R., Arutla, V., & Srivenugopal, K. S. (2018) · Carcinogenesis · doi:10.1093/carcin/bgy093 · Cited by 16
Retractedvan Zelm, M. C., Pumar, M., Shuttleworth, P., Aui, P. M., Smart, J. M., Grigg, A., & Bosco, J. J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00895 · Cited by 16
“Cytogenetics revealed a complex karyotype with hypodiploidy resulting in near triploidy and mutation analysis demonstrated the presence of the dominant negative TP53 R273H missense mutation at 100% variant frequency (17, 18).”
BackgroundKim, D., Han, S. K., Lee, K., Kim, I., Kong, J., & Kim, S. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz536 · Cited by 15
Thomas, J. P., Loke, Y. K., & Alexandre, L. (2020) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-020-02967-0 · Cited by 17
“Mutant TP53, themost frequentlymutated gene in cancer [7, 8] and consistently associated with poor prognosis [9], has been shown to upregulate transcription of mevalonate pathway products to sustain malignant proliferation [10], a pathway potently inhibited by statins.”
BackgroundGene Regulation by p53 in Human Cancer System
Ghosh, S., Bhattacharjee, M., & Jana, N. K. (2022) · Asian Pacific Journal of Cancer Biology · doi:10.31557/apjcb.2022.7.1.97-109 · Cited by 16
“It is also reported that one p53 mutant behaves differently than other mutants based on their confirmation, binding pattern, cellular localization, or transactivation capacity through p53 gain of function R248W, R273H, R273C, R282W) over large evolutionary timescales [31].”
BackgroundZhang, S., Zhang, R., Guo, D., Han, Y., Song, G., Yang, F., & Chen, Y. (2022) · Environment International · doi:10.1016/j.envint.2022.107292 · Cited by 16
Yan, J., Menéndez, D., Yang, X.-P., Resnick, M. A., & Jetten, A. M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.013102 · Cited by 16
Wallentine, B. D., Wang, Y., Tretyachenko-Ladokhina, V., Tan, M., Senear, D. F., & Luecke, H. (2013) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444913020830 · Cited by 16
“Statistical analysis shows that about half of all human tumors carry mutant p53 alleles, about 70% of which are single-site missense mutations located in the core domain (IARC TP53 Database, version R16; http:// p53.iarc.fr; Vousden & Lu, 2002; Petitjean et al., 2007).”
BackgroundGrawenda, A. M., Møller, E. K., Lam, S., Repapi, E., Teunisse, A. F. A. S., Alnæs, G. I. G., Børresen‐Dale, A., Kristensen, V. N., Goding, C. R., Jochemsen, A. G., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-2637 · Cited by 16
Camerini, A., Donati, S., Viacava, P., Siclari, O., PUCCETTI, C., Tartarelli, G., Valsuani, C., Luca, F. D., Martini, L., Cavazzana, A. O., et al. (2011) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-30-38 · Cited by 16
“demonstrated in numerous studies to be a prognostic factor in BC [11-17] and that it may determine the sensitivity to specific therapeutic agents [18-22].”
BackgroundLifestyle factors and p53 mutation patterns in colorectal cancer patients in the EPIC-Norfolk study
Park, J. Y., Mitrou, P. N., Keen, J., Dahm, C. C., Gay, L. J., Luben, R., McTaggart, A., Khaw, K., Ball, R. Y., Arends, M. J., et al. (2010) · Mutagenesis · doi:10.1093/mutage/geq012 · Cited by 16
Long, J., Zhang, Z., Liu, Z., Xu, Y., & Ge, C. (2015) · Oncology Letters · doi:10.3892/ol.2015.4042 · Cited by 16
“Presently, TP53 is the most frequently mutated gene in human cancer and its mutation frequency is up to 96% in pancreatic adenocarcinoma (28,29).”
Backgroundp53 family interactions and yeast: together in anticancer therapy
Gomes, S., Leão, M., Raimundo, L., Ramos, H., Soares, J., & Saraiva, L. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2016.02.007 · Cited by 18
Fitarelli-Kiehl, M., Macedo, G. S., Schlatter, R. P., Koehler‐Santos, P., Matte, Ú. D. S., Ashton‐Prolla, P., & Giacomazzi, J. (2016) · Genetics and Molecular Biology · doi:10.1590/1678-4685-gmb-2014-0351 · Cited by 16
“PCR was performed using primers and conditions previously described (primer sequences and PCR conditions are available at http://p53.iarc.fr/Download/ TP53_DirectSequencing_IARC.pdf; Petitjean et al., 2007) and then treated with 10 U of Exonuclease I and 0.5 U of Shrimp Alkaline Phosphatase (Fermentas), and incubated…”
MethodInfluentialp53, p63 and p73 in the wonderland ofS. cerevisiae
Billant, O., Blondel, M., & Voisset, C. (2017) · Oncotarget · doi:10.18632/oncotarget.18506 · Cited by 16
“The progressive identification and characterization of p53 mutations led to the description of seven mutational hotspots, which are most frequently found in tumors [4].”
BackgroundAnalysis of mutational signatures in C. elegans: Implications for cancer genome analysis
Meier, B., Volkova, N. V., Gerstung, M., & Gartner, A. (2020) · DNA repair · doi:10.1016/j.dnarep.2020.102957 · Cited by 17
Hall, J. A., Marcel, V., Bolin, C. M., Fernet, M., Tartier, L., Vaslin, L., & Hainaut, P. L. (2009) · Biochemical Society Transactions · doi:10.1042/bst0370527 · Cited by 16
Self-citationMartínez‐Cruz, A. B., Santos, M., García‐Escudero, R., Moral, M., Segrelles, C., Lorz, C., Sáiz-Ladera, C., Buitrago-Pérez, Á., Costa, C., & Paramio, J. M. (2009) · PubMed · Cited by 16
Li–Fraumeni syndrome presenting as mucosal melanoma: Case report and treatment considerations
Klein, J. D., & Kupferman, M. E. (2016) · Head & Neck · doi:10.1002/hed.24594 · Cited by 16
“other cases, 1 of which was a hematologic malignancy and none of which were melanoma.(11,12) There are reports of uveal and cutaneous melanoma with TP53 mutations, but no reports of germline TP53 mutations associated with mucosal melanoma have been published to date.”
BackgroundOrnellas, A. A., Alves, G., & Schwindt, A. B. D. S. (2014) · Springer eBooks · doi:10.1007/978-1-4939-0461-7_4 · Cited by 17
What do we need to know and understand about p53 to improve its clinical value?
Salomao, N., Karakostis, K., Hupp, T., Vollrath, F., Vojtesek, B., & Fahraeus, R. (2021) · The Journal of Pathology · doi:10.1002/path.5677 · Cited by 15
“This is illustrated by the frequency at which p53 (TP53) mutations appear in cancers, varying greatly: from few of acute myeloid leukaemias and renal cancers tomore frequent in breast, ovarian, bone and soft tissue sarcomas, brain tumours, and adrenocortical carcinomas (ADCs) [1].”
BackgroundWei, Y., Yang, X., Gao, L., Xu, Y., & Cheng, Y. (2022) · Translational Oncology · doi:10.1016/j.tranon.2022.101385 · Cited by 15
Schaefer, K. N., Geil, W. M., Sweredoski, M. J., Moradian, A., Hess, S. Y., & Barton, J. K. (2015) · Biochemistry · doi:10.1021/bi501424v · Cited by 16
Kouidou, S., Malousi, A., & Maglaveras, N. (2009) · Molecular Carcinogenesis · doi:10.1002/mc.20537 · Cited by 15
Kim, M. C., Choi, J. E., Lee, S. J., & Bae, Y. K. (2016) · Annals of Surgical Oncology · doi:10.1245/s10434-016-5307-z · Cited by 15
“mutated gene in human cancers, and *30% of breast cancers display TP53 mutation.(18,19) The frequency of this mutation is dependent on breast cancer molecular subtype, for example, lowest mutation frequency is observed in the luminal subtype and highest in the basal subtype.”
BackgroundEarly and consistent overexpression of ADRM1 in ovarian high-grade serous carcinoma
Jiang, R. T., Yemelyanova, A. V., Xing, D., Anchoori, R. K., Hamazaki, J., Murata, S., Seidman, J. D., Wang, T., & Roden, R. B. S. (2017) · Journal of Ovarian Research · doi:10.1186/s13048-017-0347-y · Cited by 15
“Indeed TP53 is mutated in nearly all high grade serous carcinomas (HGSC), the histotype responsible for most deaths from ovarian cancer [5, 6], and is also mutated in its precursor, serous tubal intraepithelial carcinoma (STIC) [7–9], suggesting this is a key and early event in carcinogenesis [10].”
BackgroundSmiles, W. J., & CAMERA, D. M. (2017) · Acta Physiologica · doi:10.1111/apha.13004 · Cited by 15
“Discovered in the late 1970s as a potent tumour suppressor, p53 is commonly mutated in human cancers and has been appropriately named “Guardian of the Genome”.1,2 p53 preserves genomic integrity through several DNA damage surveillance mechanisms, including its ability to induce transient cell cycle arrest for the repa…”
BackgroundOmar, S. I., & Tuszyński, J. A. (2018) · Oncotarget · doi:10.18632/oncotarget.26440 · Cited by 15
“Two of the highest frequency p53 mutant proteins, are R175H and R273H mp53, which differ from the wt protein sequence by a single missense mutation of the DNA binding domain arginine residues at positions 175 and 273 to histidine, respectively [7, 8].”
BackgroundStahlecker, J., Klett, T., Schwer, M., Jaag, S., Dammann, M., Ernst, L. N., Braun, M. B., Zimmermann, M. O., Krämer, M., Lämmerhofer, M., et al. (2022) · RSC Medicinal Chemistry · doi:10.1039/d2md00246a · Cited by 15
TP53 mutation profile of esophageal squamous cell carcinomas of patients from Southeastern Brazil
Rossini, A., Simão, T. D. A., Marques, C. B., Soares‐Lima, S. C., Herbster, S., Rapozo, D. C. M., Andreollo, N. A., Ferreira, M. A., El-Jaick, K. B., Teixeira, R. A. P., et al. (2009) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2009.11.005 · Cited by 15
Roles of p53 and p16 in triple-negative breast cancer
Dang, D. N., & Peng, Y. S. (2013) · Breast Cancer Management · doi:10.2217/bmt.13.59 · Cited by 15
Miller-Samuel, S., Macdonald, D., Weitzel, J., Santiago, F., Martino, M., Namey, T., Augustyn, A., Mueller, R., Forman, A., Bradbury, A., et al. (2011) · Seminars in Oncology · doi:10.1053/j.seminoncol.2011.04.008 · Cited by 15
Ramalho, E. A., Silva-Filho, J. L., Cartaxo, M. F. D. S., Cavalcanti, C. D. L. B., Rêgo, M. J. B. D. M., Oliveira, M. B., & Beltrão, E. I. U. F. D. P. (2014) · Biological Research · doi:10.1186/0717-6287-47-3 · Cited by 15
“DNA methylation is an important epigenetic mechanism that occurs in CpG sites and is directly involved in gene regulation [18-22].”
BackgroundVitto, H. D., Mendonça, B. D. S., Elseth, K. M., Onul, A., Xue, J., Vesper, B. J., Gallo, C. V. D. M., Rumjanek, F. D., Paradise, W. A., & Radosevich, J. A. (2012) · Tumor Biology · doi:10.1007/s13277-012-0564-3 · Cited by 15
“The L194F point mutation has been reported as a somatic mutation in 27 tumors as a germline mutation in families with Li–Fraumeni syndromes [21].”
BackgroundMethodInfluentialImpact of the p53 status of tumor cells on extrinsic and intrinsic apoptosis signaling
Wachter, F., Grunert, M., Blaj, C., Weinstock, D. M., Jeremias, I., & Ehrhardt, H. (2013) · Cell Communication and Signaling · doi:10.1186/1478-811x-11-27 · Cited by 15
Saxena, A., Shukla, S. K., Prasad, K. N., & Ghoshal, U. C. (2012) · Europe PMC (PubMed Central) · Cited by 15
Kim, M., Lee, M., Lee, A., Choi, B., Park, W. C., Kim, S. H., Lee, J., & Kang, J. K. (2025) · Histopathology · doi:10.1111/his.15453 · Cited by 14
“25,26”
DNA damage response proteins in canine cancer as potential research targets in comparative oncology
Suárez, B. H., Gillespie, D. A., & Pawlak, A. (2021) · Veterinary and Comparative Oncology · doi:10.1111/vco.12795 · Cited by 15
“cancer is clear and a loss of wild type tp53 expression or tumour suppressor function is frequently linked to malignant transformation.(41) In addition, when tp53 is mutated, it can gain oncogenic functions and facilitate cell transformation and tumorigenesis.”
BackgroundA role for bioinorganic chemistry in the reactivation of mutant p53 in cancer
Miller, J. J., Kwan, K., Gaiddon, C., & Storr, T. (2022) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-022-01939-2 · Cited by 14
Song, B., Wang, J., Ren, Y., Su, Y.-N., Geng, X., Yang, F., Wang, H., & Zhang, J. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114773 · Cited by 14
RetractedLi, J., Guo, M., Chen, L., Chen, Z., Fu, Y., & Chen, Y. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06429-8 · Cited by 15
“No mycoplasma contamination was detected.”
Kállai, A., Ungvari, A., Csabán, D., Őrfi, Z., Lehoczki, A., Harasztdombi, J., Yabluchanskiy, A., Benyó, Z., Szappanos, Á., Tarantini, S., et al. (2025) · GeroScience · doi:10.1007/s11357-025-01654-1 · Cited by 14
Association of TP53 polymorphisms on the risk of Wilms tumor
Andrade, R. C., Cardoso, L. C. A., Ferman, S., Faria, P. S., Seuánez, H. N., Achatz, M. I., & Vargas, F. R. (2013) · Pediatric Blood & Cancer · doi:10.1002/pbc.24775 · Cited by 14
Pathways Contributing to Development of Spontaneous Mammary Tumors in BALB/c-Trp53+/− Mice
Yan, H., Blackburn, A. C., McLary, S. C., Tao, L., Roberts, A. L., Xavier, E. A., Dickinson, E. S., Seo, J. H., Arenas, R. B., Otis, C. N., et al. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090438 · Cited by 13
Kucab, J. E., Zwart, E., STEEG, H. V., Luijten, M., Schmeiser, H. H., Phillips, D. H., & Arlt, V. M. (2015) · DNA repair · doi:10.1016/j.dnarep.2015.11.004 · Cited by 14
“Over 28,000 TP53 mutations detected in human tumours have been catalogued in the IARC TP53 mutation database [21].”
BackgroundComplex analysis of the p53 tumor suppressor in lung carcinoma
Šmardová, J., Lišková, K., Ravčuková, B., Malčíková, J., Hausnerová, J., Svitáková, M., Hrabálková, R., Zlámalíková, L., Kozubík, K. S., Blaháková, I., et al. (2015) · Oncology Reports · doi:10.3892/or.2015.4533 · Cited by 14
TP53 germline and somatic mutations in a patient with fibrolamellar hepatocellular carcinoma
Andrade, R. C., Lima, M. A. F. D., de Faria, P. A. S., & Vargas, F. R. (2017) · Familial Cancer · doi:10.1007/s10689-017-9998-5 · Cited by 14
Nb-induced stabilisation of p53 in HPV-infected cells
Steels, A., Vannevel, L., Zwaenepoel, O., & Gettemans, J. (2019) · Scientific Reports · doi:10.1038/s41598-019-49061-9 · Cited by 15
Xie, F., Gleue, C. A., Deschaine, M. A., Dasari, S., Lau, J. S., Sartori‐Valinotti, J. C., Meves, A., & Lehman, J. S. (2022) · Journal of Oral Pathology and Medicine · doi:10.1111/jop.13284 · Cited by 14
Arciello, M., Longo, A., Viscomi, C., Capo, C. R., Angeloni, A., Rossi, L. C., & Balsano, C. (2015) · BioMetals · doi:10.1007/s10534-015-9886-0 · Cited by 14
Novel oncogene amplifications in tumors from a family with Li–Fraumeni syndrome
Rieber, J., Remke, M., Hartmann, C. J., Korshunov, A., Burkhardt, B., Sturm, D., Mechtersheimer, G., Wittmann, A., Greil, J., Blattmann, C., et al. (2009) · Genes Chromosomes and Cancer · doi:10.1002/gcc.20665 · Cited by 14
“Up to now, about 390 different TP53 germline mutations have been described in 388 families or individuals (Petitjean et al., 2007).”
BackgroundInfluentialLindley, R. A., & Steele, E. J. (2013) · ISRN Genomics · doi:10.1155/2013/921418 · Cited by 18
“e data analysed here was extracted from this source [47] (http://www-p53.”
MethodCorrêa, G. T. B., Bernardes, V. F., de Sousa, S. F., Diniz, M. G., Salles, J. M. P., de Souza, R. P., de Paula, A. M. B., Gomez, R. S., & Gomes, C. C. (2015) · Tumor Biology · doi:10.1007/s13277-015-3659-9 · Cited by 14
“The human tumor suppressor gene, TP53 is mutated in about 50 % of human cancer samples [34].”
BackgroundA Meta-Analysis of Biomarkers for the Prognosis of Triple-Negative Breast Cancer Patients
Gui, Y., Xu, S., Yang, X., Gu, L., Zhang, Z., Luo, X., & Chen, L. (2016) · Biomarkers in Medicine · doi:10.2217/bmm-2015-0064 · Cited by 14
Abramowitz, J., Neuman, T., Perlman, R., & Ben‐Yehuda, D. (2017) · BMC Medical Genomics · doi:10.1186/s12920-017-0249-2 · Cited by 14
“1% of the cases according to version R15 of the IARC database [16].”
BackgroundBhagavatula, G., Rich, M. S., Young, D. L., Marin, M. G., & Fields, S. (2017) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-17-0245 · Cited by 15
“Themajority of exon 6 synonymous mutations found in the COSMIC database were from carcinoma samples, a cancer type in which dominant negative p53 mutations are common (28).”
McGowan, E. M., Lin, Y., & Hatoum, D. (2018) · Cancers · doi:10.3390/cancers10060172 · Cited by 14
The role of telomere shortening in carcinogenesis: A hybrid stochastic-deterministic approach
Rodriguez-Brenes, I. A., Komarova, N. L., & Wodarz, D. (2018) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2018.09.003 · Cited by 12
Gislinge, J. I. P., Klausen, P. H., Toxværd, A., Abedi, A. A., Kovacevic, B., Karstensen, J., Poulsen, T. S., Kalaitzakis, E., Høgdall, E. V. S., & Vilmann, P. (2019) · Endoscopic Ultrasound · doi:10.4103/eus.eus_36_19 · Cited by 15
Shen, C., Cheng, W.-Y., Lee, C.-H., Dai, X., Chiao, M., Liang, Y.-J., Hsieh, W.-Y., Mao, T.-F., Lin, G.-S., Chen, S.-R., et al. (2020) · BMC Cancer · doi:10.1186/s12885-020-07210-8 · Cited by 15
McBride, K. A., Hallowell, N., Tattersall, M. H. N., Kirk, J., Ballinger, M. L., Thomas, D. M., Mitchell, G., & Young, M. (2015) · Journal of Community Genetics · doi:10.1007/s12687-015-0231-7 · Cited by 14
p53-targeted cancer pharmacotherapy: move towards small molecule compounds
Kim, S.-H., & Dass, C. R. (2011) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.2010.01248.x · Cited by 14
“fr),([92]) most mutations have common features that would make restoring wild-type p53 functions feasible.”
BackgroundRichardson, E., Stockwell, S. R., Li, H., Aherne, W., Cuomo, M. E., & Mittnacht, S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031627 · Cited by 13
“However, nearly 70% of all cancers express wt TP53, and demonstrate competence for DNA damageassociated TP53 signalling [81].”
BackgroundMdm4 loss in mice expressing a p53 hypomorph alters tumor spectrum without improving survival
Fang, M., Simeonova, I., Bardot, B., Lejour, V., Jaber, S., Bouarich-Bourimi, R., Morin, A., & Toledo, F. (2013) · Oncogene · doi:10.1038/onc.2013.62 · Cited by 15
Olivier, M., Petitjean, A., Teague, J. W., Forbes, S. A., Dunnick, J. K., den Dunnen, J. T., Langerød, A., Wilkinson, J. M., Vihinen, M., Cotton, R. G. H., et al. (2008) · Human Mutation · doi:10.1002/humu.20832 · Cited by 14
“Graphical and tabular tools allow the analysis of cancer-specific and/or population-specific mutation prevalences and patterns, as well as prognostic and predictive value of specific mutations [Petitjean et al., 2007].”
BackgroundMethodSelf-citationNavas, M. C., Mellado, I. S., Carreño, A. M. G., Uribe, D., Ríos‐Ocampo, W. A., Cortés-Mancera, F., Martel‐Planche, G., Vieco, B., Lozano, D., Jiménez, C., et al. (2011) · Hepatitis Research and Treatment · doi:10.1155/2011/582945 · Cited by 14
“G : C → T : A have been detected in HCC [36], whereby this mutation could be a biomarker for dietary exposure to anatoxin.”
BackgroundMethodSelf-citationKlett, T., Stahlecker, J., Jaag, S., Masberg, B., Knappe, C., Lämmerhofer, M., Coles, M. P., Stehle, T., & Boeckler, F. M. (2024) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.4c00414 · Cited by 14
Floris, M., Pira, G., Castiglia, P., Idda, M. L., Steri, M., Miglio, M. R. D., Piana, A. F., Cossu, A., Azara, A., Arru, C., et al. (2022) · Oncology Letters · doi:10.3892/ol.2022.13451 · Cited by 12
“On the other hand, the P72 variant has greater binding affinity with the transcriptional machinery to activate transcription, inducing higher levels of arrest in G1 phase and facilitating repair of damaged DNA (42‐44) TP53 is a tumor suppressor gene that, under normal conditions, exerts its protective role via activat…”
BackgroundGenetic Signature of Human Pancreatic Cancer and Personalized Targeting
Reshkin, S. J., Cardone, R. A., & Koltai, T. (2024) · Cells · doi:10.3390/cells13070602 · Cited by 14
“A total of 32.6% of PDAC patients (299 TP53 mutated cases in 918 pancreatic tumors) have an inactivating TP53 mutation according to the IARC (International Agency for Research on Cancer, WHO) TP53 Database (R13, November 2008) [161].”
MethodInfluentialTP53 mutation analysis in chronic lymphocytic leukemia: comparison of different detection methods
Kantorová, B., Malčíková, J., Šmardová, J., Pavlová, Š., Trbušek, M., Tom, N., Plevová, K., Tichý, B., Truong, S., Divíšková, E., et al. (2014) · Tumor Biology · doi:10.1007/s13277-014-2971-0 · Cited by 13
“, in lung or urinary tract cancers [19, 27].”
BackgroundMethodResultInfluentialTowards linked open gene mutations data
Zappa, A., Splendiani, A., & Romano, P. D. (2012) · BMC Bioinformatics · doi:10.1186/1471-2105-13-s4-s7 · Cited by 13
“The database compiles all TP53 mutations that have been reported in the published literature since 1989 [35].”
BackgroundKato, K., Oh, Y., Takita, J., Gunji, Y., Kobayashi, C., Yoshimi, A., Nakao, T., Noma, M., Koike, K., Morimoto, A., et al. (2015) · International Journal of Hematology · doi:10.1007/s12185-015-1895-9 · Cited by 13
“fr/), this alteration has no effect of p53 transactivation activity [19].”
BackgroundAdaptive regulation of glucose transport, glycolysis and respiration for cell proliferation
Toyoda, Y., & Saitoh, S. (2015) · BioMolecular Concepts · doi:10.1515/bmc-2015-0018 · Cited by 13
“Considering a wide range of functions of p53 in cellular processes, it is reasonable that more than half of all malignant cancers show a defect in p53 (34, 35).”
BackgroundOhnami, S., Ohshima, K., Nagashima, T., Urakami, K., Shimoda, Y., Saito, J., Naruoka, A., Hatakeyama, K., Mochizuki, T., Serizawa, M., et al. (2017) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-017-2977-1 · Cited by 13
“A database of TP53 mutations is available [6, 7], and there are detailed data regarding the functional activities of TP53 mutants.”
BackgroundSandoval, J. E., & Reich, N. O. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.010827 · Cited by 14
“for mutations in a wide-range of human cancers, there is growing interest in understanding how mutations in p53 contribute to disease onset and progression (30, 31).”
BackgroundMessaoudi, S. A., Sharhan, N. A., Alharthi, B. N., Babu, S. R., Alsaleh, A. B., Alasiri, A. M., Assidi, M., Buhmeida, A. S., & Almawi, W. Y. (2022) · Biomedical Reports · doi:10.3892/br.2022.1509 · Cited by 13
Mafune, A., Hama, T., Suda, T., Suzuki, Y., Ikegami, M., Sakanashi, C., Imai, S., Nakashima, A., Yokoo, T., Wada, K., et al. (2015) · BMC Cancer · doi:10.1186/s12885-015-1220-2 · Cited by 13
“[21].”
LONG, J., Wang, Y., Li, M., Tong, W., Jia, J., & Huang, J. (2013) · Oncology Reports · doi:10.3892/or.2013.2430 · Cited by 13
The Roche Cancer Genome Database (RCGDB)
Küntzer, J., Eggle, D., Lenhof, H., BURTSCHER, H. J., & Klostermann, S. (2010) · Human Mutation · doi:10.1002/humu.21207 · Cited by 13
“…databases, we integrate single-gene locus-specific databases like the L1CAM mutation database from the university of Groningen [Van et al., 1996] and the IARC P53 mutation database [Petitjean et al., 2007], with all TP53 gene variations identified in human populations and tumor samples.”
MethodCreation and preliminary characterization of a Tp53 knockout rat
McCoy, A., Besch-Williford, C. L., Franklin, C. L., Weinstein, E. J., & Cui, X. (2012) · Disease Models & Mechanisms · doi:10.1242/dmm.009704 · Cited by 15
“…including gene disruptions (Donehower et al., 1992; Jacks et al., 1994), humanization of the DNA binding domain (Luo et al., 2001) and a variety of point mutations (Petitjean et al., 2007), demonstrating good correlation between decreased TP53 activity and increased incidences of tumor formation.”
Backgroundder Vorst, S. V., Dekairelle, A., Weynand, B., Hamoir, M., & Gala, J. (2011) · Head & Neck · doi:10.1002/hed.21960 · Cited by 13
“It is worth noting that the relative rate of deletions or insertions identified with FASAY in our HNSCC samples (16% and 5%, respectively) was in agreement with the literature (14% and 3%, respectively).(57) In contrast, positive nuclear p53 staining without TP53 mutation may result from p53 protein stabilization cons…”
BackgroundResultTaylor, N. J., Nikolaishvili‐Feinberg, N., Midkiff, B. R., Conway, K., Millikan, R. C., & Geradts, J. (2015) · Applied immunohistochemistry & molecular morphology · doi:10.1097/pai.0000000000000207 · Cited by 13
Kazantseva, M., Hung, N. A., Mehta, S. Y., Roth, I. M., Eiholzer, R. A., Rich, A. M., Seo, B., Baird, M. A., Braithwaite, A. W., & Slatter, T. L. (2017) · Scientific Reports · doi:10.1038/s41598-017-01800-6 · Cited by 13
Irradiation induces p53 loss of heterozygosity in breast cancer expressing mutant p53
Ghaleb, A. M., Yallowitz, A. R., & Marchenko, N. D. (2019) · Communications Biology · doi:10.1038/s42003-019-0669-y · Cited by 13
Wang, H., Chen, L., Zhou, T., Zhang, Z., & Zeng, C. (2020) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.0c00119 · Cited by 13
MicroRNA-324-5p–CUEDC2 Axis Mediates Gain-of-Function Mutant p53-Driven Cancer Stemness
Ghatak, D., Datta, A., Roychowdhury, T., Chattopadhyay, S., & Roychoudhury, S. (2021) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-20-0717 · Cited by 13
Olivier, M. (2015) · Springer eBooks · doi:10.1007/978-3-642-27841-9_2934-3 · Cited by 13
Self-citationSilva, J. L., de Andrade, G. C., Petronilho, E. C., de Sousa, G. D. S., Mota, M. F., Quarti, J., Guedes-da-Silva, F. H., Ferretti, G. D. S., Rangel, L. P., Vieira, T. C. R. G., et al. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70055 · Cited by 12
“In contrast, conformational mutations destabilize p53's DBD structure to varying degrees (e.g., R175H and R282W, which are partially unfolded, and G245S and R249S, which display local structural changes near the mutation site) (Bullock et al. 2000; Petitjean et al. 2007).”
Anticancer therapeutic strategies for targeting mutant p53-Y220C
Chasov, V. V., Davletshin, D., Gilyazova, E., Mirgayazova, R., Kudriaeva, A. A., Khadiullina, R., Yuan, Y., & Bulatov, E. (2023) · Journal of Biomedical Research · doi:10.7555/jbr.37.20230093 · Cited by 13
Metadata
- 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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