The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation
Open accessAbstract
The TP53 gene is frequently mutated in human cancer. Research has focused predominantly on six major "hotspot" codons, which account for only ∼30% of cancer-associated p53 mutations. To comprehensively characterize the consequences of the p53 mutation spectrum, we created a synthetically designed library and measured the functional impact of ∼10,000 DNA-binding domain (DBD) p53 variants in human cells in culture and in vivo. Our results highlight the differential outcome of distinct p53 mutations in human patients and elucidate the selective pressure driving p53 conservation throughout evolution. Furthermore, while loss of anti-proliferative functionality largely correlates with the occurrence of cancer-associated p53 mutations, we observe that selective gain-of-function may further favor particular mutants in vivo. Finally, when combined with additional acquired p53 mutations, seemingly neutral TP53 SNPs may modulate phenotypic outcome and, presumably, tumor progression.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“This heterogeneity also extends to the biological activity of the majority of mutant p53 proteins, as demonstrated by the various multiplex assays of variant effect conducted on over 10,000 p53 variants [32, 33, 34, 35].”
From The TP53 tumor suppressor gene: From molecular biology to clinical investigations (2025) · cites this paper as [33]
In the citing paper
“Various saturation mutagenesis studies, with substitutions at every position in this domain, have demonstrated that these changes lead to partial or total loss of DNA binding activity [32, 33, 34, 35].”
From The TP53 tumor suppressor gene: From molecular biology to clinical investigations (2025) · cites this paper as [33]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
TP53 mutations in human cancers: origins, consequences, and clinical use.
Olivier, M., Hollstein, M., & Hainaut, P. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001008 · Cited by 2,199
The first 30 years of p53: growing ever more complex.
Levine, A. J., & Oren, M. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2723 · Cited by 1,967
Self-citationTranscriptional control of human p53-regulated genes
Riley, T., Sontag, E., Chen, P., & Levine, A. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2395 · Cited by 1,921
Deep mutational scanning: a new style of protein science
Fowler, D. M., & Fields, S. (2014) · Nature Methods · doi:10.1038/nmeth.3027 · Cited by 1,287 · cited 1×
“Deep mutational scanning (Fowler and Fields, 2014) offers a high-throughput approach for revealing the consequences of genetic variation both in regulatory and coding sequences (Brenan et al.”
When mutants gain new powers: News from the mutant p53 field
Brosh, R., & Rotter, V. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2693 · Cited by 1,132
Mutation effects predicted from sequence co-variation
Hopf, T. A., Ingraham, J. B., Poelwijk, F. J., Schärfe, C. P. I., Springer, M., Sander, C., & Marks, D. S. (2017) · Nature Biotechnology · doi:10.1038/nbt.3769 · Cited by 775
Tewhey, R., Kotliar, D., Park, D. S., Liu, B., Winnicki, S., Reilly, S. K., Andersen, K. G., Mikkelsen, T. S., Lander, E. S., Schaffner, S. F., et al. (2016) · Cell · doi:10.1016/j.cell.2016.04.027 · Cited by 480
Systematic discovery of cap-independent translation sequences in human and viral genomes
Weingarten-Gabbay, S., Elias-Kirma, S., Nir, R., Gritsenko, A. A., Stern-Ginossar, N., Yakhini, Z., Weinberger, A., & Segal, E. (2016) · Science · doi:10.1126/science.aad4939 · Cited by 334
Self-citationMenendez, D., Inga, A., & Resnick, M. A. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.6.2297-2308.2006 · Cited by 81
Cited by
Disease variant prediction with deep generative models of evolutionary data
Frazer, J., Notin, P., Dias, M., Gomez, A., Min, J. K., Brock, K., Gal, Y., & Marks, D. S. (2021) · Nature · doi:10.1038/s41586-021-04043-8 · Cited by 791
Self-citationSequence modeling and design from molecular to genome scale with Evo
Nguyen, E., Poli, M., Durrant, M. G., Kang, B., Katrekar, D., Li, D. B., Bartie, L. J., Thomas, A. W., King, S. H., Brixi, G., et al. (2024) · Science · doi:10.1126/science.ado9336 · Cited by 580
A dominant-negative effect drives selection of TP53 missense mutations in myeloid malignancies
Boettcher, S., Miller, P. G., Sharma, R., McConkey, M., Leventhal, M., Krivtsov, A. V., Giacomelli, A. O., Wong, W., Kim, J., Chao, S., et al. (2019) · Science · doi:10.1126/science.aax3649 · Cited by 441
(2023) · doi:10.1101/2023.12.07.570727 · Cited by 207
Self-citationThe road ahead in genetics and genomics
McGuire, A. L., Gabriel, S., Tishkoff, S. A., Wonkam, A., Chakravarti, A., Furlong, E. E. M., Treutlein, B., Meissner, A., Chang, H. Y., López-Bigas, N., et al. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-0272-6 · Cited by 188
Self-citation
Metadata
- Authors
- Kotler, E., Shani, O., Goldfeld, G., Lotan-Pompan, M., Tarcic, O., Gershoni, A., Hopf, T. A., Marks, D. S., Oren, M., & Segal, E.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 71
- Issue
- 1
- Pages
- 178-190.e8
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2868860358
- Cited by
- 285
- References
- 9
- FWCI
- 8.76
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation. https://app.cochat.ai/papers/10.1016/j.molcel.2018.06.012
- The paper
- Kotler, E., Shani, O., Goldfeld, G., Lotan-Pompan, M., Tarcic, O., Gershoni, A., Hopf, T. A., Marks, D. S., Oren, M., & Segal, E. (2018). A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation. Molecular Cell. https://doi.org/10.1016/j.molcel.2018.06.012
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
