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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
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“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].”
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“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
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“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
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“Studies in mouse models of LFS have reported evidence of GOF for R175H and R273H mutants [Lang et al., 2004; Olive et al., 2004].”
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“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.”
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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.”
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Items 401–500 of 999
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BackgroundP53 transcriptional activities: A general overview and some thoughts
Millau, J., Bastien, N., & Drouin, R. (2008) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2008.06.002 · Cited by 65
Characterization of human breast cancer cell lines for the studies on p53 in chemical carcinogenesis
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P53 gene polymorphisms and breast cancer risk in Arab women
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“Mutations in p53 gene that cause dramatic defects in p53 function are widely detected in breast cancer and are correlated with clinical phenotypes [3].”
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YEATS4 Is a Novel Oncogene Amplified in Non–Small Cell Lung Cancer That Regulates the p53 Pathway
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“Inactivation of the p53 pathway is one of the most frequent alterations in lung cancer, with somatic mutations occurring in approximately 50% of all cases (28, 33).”
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“Previous studies have shown that these mutated alleles are expressed, but have abnormal transcriptional activity and loss of p53 tumor suppressor function (36).”
BackgroundUnravelling mechanisms of cisplatin sensitivity and resistance in testicular cancer
Koster, R., van Vugt, M. A. T. M., Timmer‐Bosscha, H., Gietema, J. A., & de Jong, S. (2013) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2013.13 · Cited by 58
Molecular and Cellular Mechanisms of Myelodysplastic Syndrome: Implications on Targeted Therapy
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Genetic landscape of T- and NK-cell post-transplant lymphoproliferative disorders
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The Status of p53 Oligomeric and Aggregation States in Cancer
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Structural and Functional Basis for Therapeutic Modulation of p53 Signaling
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“Various sequencing technologies and protocols are in useworldwide, and there is evidence for dramatic variations in the sensitivity and specificity of these methods (Petitjean et al., 2007; Edlund et al., 2012; Soussi et al., 2006).”
BackgroundMethodInfluentialPTEN: a default gate-keeping tumor suppressor with a versatile tail
Wang, X., & Jiang, X. (2008) · Cell Research · doi:10.1038/cr.2008.83 · Cited by 56
Ståhl, P. L., Stranneheim, H., Asplund, A., Berglund, L., Pontén, F., & Lundeberg, J. (2010) · Journal of Investigative Dermatology · doi:10.1038/jid.2010.302 · Cited by 56
Xu-Monette, Z. Y., Møller, M. B., Tzankov, A., Montes‐Moreno, S., Hu, W., Manyam, G. C., Kristensen, L., Fan, L., Visco, C., Dybkær, K., et al. (2013) · Blood · doi:10.1182/blood-2012-12-473702 · Cited by 56
Mutant p53 R248Q but not R248W enhances in vitro invasiveness of human lung cancer NCI-H1299 cells
Yoshikawa, K., Hamada, J., Tada, M., Kameyama, T., Nakagawa, K., Suzuki, Y., Ikawa, M., Hassan, N. M. M., Kitagawa, Y., & Moriuchi, T. (2010) · Biomedical Research · doi:10.2220/biomedres.31.401 · Cited by 55
“This control vector was designed to express stop codon at 84th codon (pIRES2-AcGFP1 p53 (1-83)).”
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“While it is known that tumor cell lines differ in their p53 status, all ESCC cell lines used in this study had mutanttype p53 (42).”
BackgroundSuad, O., Rozenberg, H., Brosh, R., Diskin‐Posner, Y., Kessler, N., Shimon, L. J. W., Frolow, F., Liran, A., Rotter, V., & Shakked, Z. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.10.063 · Cited by 58
Gain of function of mutant p53: R282W on the peak?
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The paradox of cancer genes in non-malignant conditions: implications for precision medicine
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“In the case of TP53 mutations, which are clearly related to the formation of multiple cancers [140], perhaps they induce the inflammatory condition rheumatoid arthritis, rather than cancer, in the synovium [37, 38].”
BackgroundInfluentialSelf-citationPTCH mutations in basal cell carcinomas from azathioprine-treated organ transplant recipients
Harwood, C. A., Attard, N. R., O’Donovan, P., Chambers, P. A., Perrett, C. M., Proby, C. M., McGregor, J. M., & Karran, P. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604665 · Cited by 56
“The IARC TP53 Somatic Mutation database lists more than 1000 mutations from normal, preneoplastic and neoplastic skin (Petitjean et al, 2007) although an association with immunosuppression is noted in only 26 cases for which the medication is not specified.”
BackgroundCharacterization of three new serous epithelial ovarian cancer cell lines
Ouellet, V., Zietarska, M., Portelance, L., Lafontaine, J., Madore, J., Puiffe, M., Arcand, S. L., Shen, Z. Z., Hébert, J., Tonin, P. N., et al. (2008) · BMC Cancer · doi:10.1186/1471-2407-8-152 · Cited by 56
“This is not inconsistent with independent reports that only a smaller fraction of cancers (about 12%) harboring nonsense mutations exhibited IHC-positivity as compared to IHC-negative nonsense mutations (IARC TP53 mutation database) [57].”
BackgroundResultThe unfolded protein response regulator GRP78 is a novel predictive biomarker in colorectal cancer
Thornton, M., Aslam, M. A., Tweedle, E. M., Ang, C. W., Campbell, F., Jackson, R., Costello, E., Rooney, P. S., Vlatković, N., & Boyd, M. T. (2013) · International Journal of Cancer · doi:10.1002/ijc.28137 · Cited by 57
Structural and sequential context of p53: A review of experimental and theoretical evidence
Saha, T., Kar, R. K., & Sa, G. (2014) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2014.12.002 · Cited by 58
Ultraslow oligomerization equilibria of p53 and its implications
Natan, E., Hirschberg, D., Morgner, N., Robinson, C. V., & Fersht, A. R. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0907840106 · Cited by 55
“T tumor suppressor p53 is a transcription factor that is inactivated by mutation in some 50% of human cancers (1, 2).”
BackgroundSahni, J. M., Gayle, S. S., Weber-Bonk, K. L., Cuellar-Vite, L., Yori, J. L., Webb, B. M., Ramos, E. K., Seachrist, D. D., Landis, M. D., Chang, J. C., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.738666 · Cited by 58
“As is typical for TNBC, TP53 (p53-encoding gene) is mutated to transcriptionally inactive isoforms in all seven cell lines tested (19).”
BackgroundHolmila, R. J., Sklias, A., Muller, D. C., Esposti, D. D., Guilloreau, P., McKay, J., Sangrajrang, S., Srivatanakul, P., Hainaut, P. L., Merle, P., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0174265 · Cited by 55
Self-citationModulation of oncogenic transcription factors by bioactive natural products in breast cancer
Hasanpourghadi, M., Pandurangan, A. K., & Mustafa, M. R. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.09.009 · Cited by 55
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“Somatic TP53 gene mutations are some of the most frequently observed in human cancers, including malignant CNS tumors (61).”
BackgroundWu, C., Zhou, L., Gong, H.-L., Du, H.-D., Tian, J., Sun, S., & Li, J. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.08.041 · Cited by 54
“Mutations in the TP53 tumor suppressor gene are found in approximately 50% of human cancers and the most common mutations are missense mutations leading to amino acid substitutions [36].”
BackgroundWood dust–related mutational profile of TP53 in intestinal-type sinonasal adenocarcinoma
Pérez‐Escuredo, J., Martínez, J. G., Vivanco, B., Marcos, C. Á., Suárez, C., Llorente, J. L., & Hermsen, M. A. J. A. (2012) · Human Pathology · doi:10.1016/j.humpath.2012.01.016 · Cited by 54
“G→A transition is the most frequent alteration in the TP53 gene with a prevalence of around 25% [25] and is mostly found in nonsmoker patients with cancer.”
BackgroundJenkins, L. M. M., Feng, H., Durell, S. R., Tagad, H. D., Mazur, S. J., Tropea, J. E., Bai, Y., & Appella, E. (2015) · Biochemistry · doi:10.1021/acs.biochem.5b00044 · Cited by 55
Germ line mutations associated with leukemias
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“Although germ line ETV6mutations are most closely associated with B-cell ALL, other hematologic malignancies have been observed in carriers, including MDS, multiple myeloma, and AML.”
BackgroundInfluentialTP53 Mutational Status and Cetuximab Benefit in Rectal Cancer: 5-Year Results of the EXPERT-C Trial
Sclafani, F., de Castro, D. G., Cunningham, D., Wilson, S. H., Peckitt, C., Tabernero, J. M., Glimelius, B. L. G., Cervantes, A. M. R., Dewdney, A., Wotherspoon, A. C., et al. (2014) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dju121 · Cited by 54
“TP53 mutations occur in approximately 50% of colorectal cancers (1) and largely result in inactivation of p53 (2).”
BackgroundTp53 status as guide for the management of ethmoid sinus intestinal-type adenocarcinoma
Bossi, P., Perrone, F., Miceli, R., Cantù, G., Mariani, L., Orlandi, E. M., Fallai, C., Locati, L. D., Cortelazzi, B., Quattrone, P., et al. (2013) · Oral Oncology · doi:10.1016/j.oraloncology.2012.12.011 · Cited by 53
Applications of computational algorithm tools to identify functional SNPs
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Evolutionary etiology of high-grade astrocytomas
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“As p53 is mutated in more than half of all cancers and inactivated by indirect mechanisms in a large proportion of the remainder (44), pathways mediating p53-independent apoptosis, such as that involving hnRNP K as demonstrated here, are appealing for therapeutic intervention.”
Backgroundp53 in head and neck cancer: Functional consequences and environmental implications of TP53mutations
Peltonen, J. K., Helppi, H. M., Pääkkö, P. K., Turpeenniemi-Hujanen, T. M., & Vähäkangas, K. (2010) · Head & Neck Oncology · doi:10.1186/1758-3284-2-36 · Cited by 55
“A combination of standard structural criteria as described by Martin et al. (2002) was also used [24].”
MethodDiffusely infiltrating astrocytomas: pathology, molecular mechanisms and markers
Ichimura, K., Narita, Y., & Hawkins, C. E. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1439-7 · Cited by 56
“Although the great majority of all TP53 mutations fall into the first category, approximately 10–20 % are either nonsense or frameshift mutations in astrocytomas, which are often found outside of the DNA-binding domain (see data from TCGA portal and The IARC TP53 Database version R17 [107]).”
The nucleoside analog clitocine is a potent and efficacious readthrough agent
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“Approximately 8% of all known p53 mutations are nonsense mutations (Petitjean et al. 2007).”
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“were verified using the International Agency for Research on Cancer (IARC) repository.(22) Single-nucleotide polymorphisms”
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Poly‐gene fusion transcripts and chromothripsis in prostate cancer
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“In fact, rs 28934574 in TP53 is a somatic mutation in 579 tumors and a germline mutation in 15 families with Li-Fraumeni syndrome (IARC TP53 database, R15) (Petitjean et al., 2007; Plon et al., 2008).”
BackgroundD’Abramo, M., Bešker, N., Desideri, A., Levine, A. J., Melino, G., & Chillemi, G. (2015) · Oncogene · doi:10.1038/onc.2015.388 · Cited by 53
Electrocatalysis in proteins, nucleic acids and carbohydrates
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“TP53 coding regions from exon 5 to 8 were analyzed by direct sequencing protocol as described in the International Agency for Research on Cancer p53 database.(24)”
p53 isoform profiling in glioblastoma and injured brain
Takahashi, R., Giannini, C., Sarkaria, J. N., Schroeder, M., Rogers, J., Mastroeni, D., & Scrable, H. J. (2012) · Oncogene · doi:10.1038/onc.2012.322 · Cited by 52
WEE1 Kinase As a Target for Cancer Therapy
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“On the other hand, besides transcription activities the mutant p53 also executes nontranscription activities.(41) Mutant p53 still caused growth arrest and mediated apoptosis independent of the transcriptional activation function.”
BackgroundTP53 mutations and SNPs as prognostic and predictive factors in patients with breast cancer (Review)
Huszno, J., & Grzybowska, E. A. (2018) · Oncology Letters · doi:10.3892/ol.2018.8627 · Cited by 52
“A total of >250 germline mutations in the TP53 gene have been described (39,40), and the most common germline mutations are missense mutations (77%).”
Applications of Recombinant Adenovirus-p53 Gene Therapy for Cancers in the Clinic in China
Xia, Y., Li, X., & Sun, W. (2020) · Current Gene Therapy · doi:10.2174/1566523220999200731003206 · Cited by 52
Yan, W., Jung, Y.-S., Zhang, Y., & Chen, X. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103497 · Cited by 53
“Missense mutations of the p53 gene, primarily clustered within the core DNA binding domain, occur in a large fraction of human tumors [1].”
BackgroundLi, Y., Gordon, M. W., Xu-Monette, Z. Y., Visco, C., Tzankov, A., Zou, D., Qiu, L., Montes‐Moreno, S., Dybkær, K., Orazi, A., et al. (2013) · Blood · doi:10.1182/blood-2012-12-471722 · Cited by 53
“Although the nucleotide length (544 bp) of exons 5 to 8 accounts for only ;46% of the coding exons (1182 bp), mutations in these exons account for 94% of all CDS somatic mutations.(19) Our analysis of TP53 CDS in the 506 DLBCL patients confirmed the uneven codon distribution of single nucleotide missense substitutions…”
BackgroundSlade, N., Moll, U. M., Brdar, B., Zorić, A., & Jelaković, B. (2009) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2009.01.005 · Cited by 50
Identification of TP53 as an acute lymphocytic leukemia susceptibility gene through exome sequencing
Powell, B. C., Jiang, L., Muzny, D. M., Treviño, L. R., Dreyer, Z. E., Strong, L. C., Wheeler, D. A., Gibbs, R. A., & Plon, S. E. (2012) · Pediatric Blood & Cancer · doi:10.1002/pbc.24417 · Cited by 51
“In the International Agency for Research on Cancer’s locus-specific database of TP53 mutations (version R15, November 2010 [17]), this mutation has been described in both germline and somatic samples.”
BackgroundGreenaway, J. B., Virtanen, C., Osz, K., Révay, T., Hardy, D. B., Shepherd, T. G., DiMattia, G. E., & Petrik, J. (2016) · Oncotarget · doi:10.18632/oncotarget.10121 · Cited by 51
“This R273H mutation in 28-2 cells is the most frequent TP53 mutation in high-grade serous ovarian cancer and accounts for 8% of all TP53 mutations [63].”
BackgroundUnsupervised detection of cancer driver mutations with parsimony-guided learning
Kumar, R. D., Swamidass, S. J., & Bose, R. (2016) · Nature Genetics · doi:10.1038/ng.3658 · Cited by 49
Clarke, J. R. S., Douglas, L. R., Duriez, P. J., Balourdas, D.-I., Joerger, A. C., Khadiullina, R., Bulatov, E., & Baud, M. G. J. (2022) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.2c00164 · Cited by 50
Genetic and Biochemical Alterations in Non-Small Cell Lung Cancer
Johnson, J. L., Pillai, S., & Chellappan, S. (2012) · Biochemistry Research International · doi:10.1155/2012/940405 · Cited by 52
“The inactivating mutations render the mutant TP53 protein unable to carry out its normal functions, that is, transcriptional transactivation of downstream target genes that regulate cell cycle and apoptosis [192].”
BackgroundKandioler, D., SCHOPPMANN, S. F., Zwrtek, R., Kappel, S., Wolf, B., Mittlböck, M., Kührer, I., Hejna, M., Pluschnig, U., Ba‐Ssalamah, A., et al. (2014) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/j.jtcvs.2014.06.079 · Cited by 50
“Mean number (range) of resected lymph nodes 17 (10-43) 16 (5-28) 16 (5-43) .”
LKB1 and Lung Cancer: More Than the Usual Suspects
Shah, U., Sharpless, N. E., & Hayes, D. N. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-6620 · Cited by 52
Vázquez, A., Grochola, L. F., Bond, E. E., Levine, A. J., Taubert, H. W., Müller, T. H., Würl, P., & Bond, G. L. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-2218 · Cited by 50
Molecular profile of oligodendrogliomas in young patients
Suri, V. S., Jha, P., Agarwal, S., Pathak, P., Sharma, M., Sharma, V., Shukla, S. K., Somasundaram, K., Mahapatra, A., Kale, S. S., et al. (2011) · Neuro-Oncology · doi:10.1093/neuonc/nor146 · Cited by 50
Leslie, P. L., Ke, H., & Zhang, Y. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.644435 · Cited by 50
“As a major factor involved in the inhibition of cell growth and division, the TP53 gene is mutated in many different types of cancer (5).”
BackgroundBastien, R. R. L., Lewis, T. B., Hawkes, J. E., Quackenbush, J. F., Robbins, T. C., Palazzo, J., Perou, C. M., & Bernard, P. S. (2008) · Human Mutation · doi:10.1002/humu.20726 · Cited by 50
Shetzer, Y., Molchadsky, A., & Rotter, V. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026203 · Cited by 53
“…(broadly described in Shetzer et al. 2014b), which is one of the reasons for the mut-p53 association with a poor prognosis (Olivier et al. 2005; Petitjean et al. 2007). mut-p53-mediated drug resistance was shown in many tumor types following treatment with different agents (Li et al. 1998;…”
BackgroundInfluentialExperimental mouse models for translational human cancer research
Zhou, Y., Xia, J., Xu, S., She, T., Zhang, Y., Sun, Y., Wen, M., Jiang, T., Xiong, Y., & Lei, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1095388 · Cited by 52
Shouse, G., Nobumori, Y., & Liu, X. (2010) · Oncogene · doi:10.1038/onc.2010.161 · Cited by 49
“However, recent data suggest that as many as 61% of lung tumors have wild-type p53 (Petitjean et al., 2007), suggesting the importance of the B56g3–p53 interaction in regulating wild-type p53 tumor suppression function.”
Mapping the p53 transcriptome universe using p53 natural polymorphs
Wang, B., Niu, D., Lam, T. H., Xiao, Z., & Ren, E. C. (2013) · Cell Death and Differentiation · doi:10.1038/cdd.2013.132 · Cited by 49
Fernández, K. S., Serinagaoglu, Y., Hammond, S., Martin, L. T., & Martin, P. T. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090405 · Cited by 49
TP53-Associated Pediatric Malignancies
Pinto, E. M., Ribeiro, R. C., de Figueiredo, B. C., & Zambetti, G. P. (2011) · Genes & Cancer · doi:10.1177/1947601911409745 · Cited by 49
Mafficini, A., Amato, E., Cataldo, I., Rusev, B. C., Bertoncello, L., Corbo, V., Simbolo, M., Luchini, C., Fassan, M., Cantù, C., et al. (2016) · Annals of Surgery · doi:10.1097/sla.0000000000001999 · Cited by 49
Olotu, F. A., & Soliman, M. E. S. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.26430 · Cited by 51
“Preponderant for p53 protein is the missense mutation, which is recorded in about 95% of p53 mutations.(5,6) These mutations at specific amino acid residues occur mostly at the core DNA binding domain (DBD) (residues 94-292) affecting six hot-spot residues (R175, G245, R248, R249, R273, R282) of the protein translatin…”
BackgroundBlakemore, S. J., Clifford, R. M., Parker, H., Antoniou, P., Stec, E., Larráyoz, M., Davis, Z. A., Kadalayil, L., Collins, A. R., Robbe, P., et al. (2020) · Leukemia · doi:10.1038/s41375-020-0723-2 · Cited by 49
Sagne, C., Marcel, V., Amadou, A., Hainaut, P. L., Olivier, M., & Hall, J. A. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.24 · Cited by 48
Self-citationRoshandel, G., Merat, S., Sotoudeh, M., Khoshnia, M., Poustchi, H., Lao‐Sirieix, P., Malhotra, S., O’Donovan, M., Etemadi, A., Nikmanesh, A., et al. (2014) · British Journal of Cancer · doi:10.1038/bjc.2014.506 · Cited by 48
“Due to the high prevalence of p53 mutation in this disease (Petitjean et al, 2007; Agrawal et al, 2012), p53 immunohistochemistry (IHC) was performed using a mouse anti-p53 antibody (DO7; Leica Biosystems, Newcastle, UK) using a fully automated IHC instrument, the Leica Bond-Max (Leica Biosystems),…”
BackgroundMethodGromyko, D., Arnesen, T., Ryningen, A., Varhaug, J. E., & Lillehaug, J. R. (2010) · International Journal of Cancer · doi:10.1002/ijc.25275 · Cited by 48
“linked to functional p53,(34,35) we sequenced the coding sequence of TP53 from all studied thyroid cell lines and checked functional status of mutated TP53 from IARC TP53 database R13 release.(36) Analysis of TP53 mutations showed that all detected mutations led to loss of p53 transactivation.”
MethodBou‐Hanna, C., Jarry, A., Lodé, L., Schmitz, I., Schulze‐Osthoff, K., Küry, S., Bezieau, S., Mosnier, J., & LABOISSE, C. L. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.01.014 · Cited by 48
Li, C., Yeh, K., Liu, W., Chen, C., Chen, D., Chen, P., & Yeh, S. (2014) · International Journal of Cancer · doi:10.1002/ijc.29052 · Cited by 48
“It is well documented that somatic mutations of p53 occur frequently in HCC and cause p53 accumulation via an increase in the stability of mutant proteins.(17) To investigate if this mechanism contributes to the increased levels of p53 observed in female HCC, we performed a sequencing analysis of all HCC samples used…”
MethodData mining using the Catalogue of Somatic Mutations in Cancer BioMart
Shepherd, R., Forbes, S. A., Beare, D. M., Bamford, S., Cole, C. G., Ward, S., Bindal, N., Gunasekaran, P., Jia, M., Kok, C. Y., et al. (2011) · Database · doi:10.1093/database/bar018 · Cited by 48
Dittmann, K., Mayer, C., Kehlbach, R., & Rodemann, H. P. (2008) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2008.01.007 · Cited by 47
“TP53, which is commonly present in many malignancies [12].”
BackgroundHaq, B. U., Qayoom, H., Sofi, S., Jan, N., Shabir, A., Ahmad, I., Ahmad, F., Almilaibary, A., & Mir, M. A. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1333447 · Cited by 47
LncRNAs: New Players in Gliomas, With Special Emphasis on the Interaction of lncRNAs With EZH2
Bian, E., Li, J., Xie, Y., Zong, G., Li, J., & Zhao, B. (2014) · Journal of Cellular Physiology · doi:10.1002/jcp.24549 · Cited by 47
“MDM2 is an E3 ubiquitin ligase to promote p53 ubiquitination, resulting in nuclear export of p53 and degradation by the proteasome, which increase cancer risk and/or accelerate tumor formation and progression (Petitjean et al., 2007; Hu et al., 2012).”
BackgroundWong, G. S., Lee, J., Park, Y.-Y., Klein–Szanto, A. J., Waldron, T. J., Cukierman, E., Herlyn, M., Gimotty, P. A., Nakagawa, H., & Rustgi, A. K. (2013) · Oncogenesis · doi:10.1038/oncsis.2013.17 · Cited by 48
Common Oncogenic Mutations Are Infrequent in Oral Squamous Cell Carcinoma of Asian Origin
Zanaruddin, S. N. S., Yee, P. S., Hor, S. Y., Kong, Y. H., Ghani, W. M. N., Mustafa, W. M. W., Zain, R. B., Prime, S. S., Rahman, Z. A. A., & Cheong, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080229 · Cited by 48
“fr/) [28].”
Yang, X., Wu, J., Lu, J., Liu, G., Di, G., Chen, C., Hou, Y., Sun, M., Yang, W., Xu, X., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125571 · Cited by 47
“One was novel and another two were detected within the germline and somatic mutations in the p53 mutation database, respectively [20] (Table 1).”
BackgroundMelanomagenesis: Overcoming the barrier of melanocyte senescence
Ha, L., Merlino, G. T., & Sviderskaya, E. V. (2008) · Cell Cycle · doi:10.4161/cc.7.13.6230 · Cited by 50
Terziyska, N., Alves, C. C., Groiß, V., Schneider, K., Farkasova, K., Ogris, M., Wagner, E., Ehrhardt, H., Brentjens, R. J., Stadt, U. Z., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052798 · Cited by 47
“cell lines might have acquired non-physiologic mutations upon prolonged culture in vitro [4].”
Pharmacologic activation of wild-type p53 by nutlin therapy in childhood cancer
Maerken, T. V., Rihani, A., Goethem, A. V., Paepe, A. D., Speleman, F., & Vandesompele, J. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.11.002 · Cited by 47
“Lung cancer 37 [6] (http://p53.”
BackgroundInfluentialSoares, J., Raimundo, L., Pereira, N. A. L., Monteiro, Â., Gomes, S., Bessa, C., Pereira, C., Queiróz, G., Bisio, A., Fernandes, J. C., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.6775 · Cited by 47
“A yeast-based screening assay, consisting of Saccharomyces cerevisiae cells expressing human wt p53 or mut p53 (R280K or Y220C; two of the most prevalent forms of human mut p53 [7]), was developed to search for mut p53 reactivators (Figure 1B).”
Courville, E. L., Yohe, S. L., Chou, D. B., Nardi, V., Lazaryan, A., Thakral, B., Nelson, A., Ferry, J. A., & Sohani, A. R. (2016) · Modern Pathology · doi:10.1038/modpathol.2016.130 · Cited by 47
The dominant-negative interplay between p53, p63 and p73: A family affair
Billant, O., Léon, A., Guellec, S. L., Friocourt, G., Blondel, M., & Voisset, C. (2016) · Oncotarget · doi:10.18632/oncotarget.11774 · Cited by 47
p53 gain‐of‐function mutations increase Cdc7‐dependent replication initiation
Datta, A., Ghatak, D., Das, S., Banerjee, T., Paul, A., Butti, R., Gorain, M., Ghuwalewala, S., Roychowdhury, A., Alam, S. K., et al. (2017) · EMBO Reports · doi:10.15252/embr.201643347 · Cited by 47
“On the basis of p53 mutation, patients were classified into two groups, patients with wildtype p53 and those with missense mutant p53 with reported gain-offunction (GOF) properties [35,53] (Dataset EV1).”
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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