Database Development

This R20 release compiles data on around 29900 somatic mutations, 9200 variants reported in SNP databases, 1530 cancer families/individual carriers of a germline mutation, 2700 cell-lines, 900 experimentally induced mutations, and functional data on over 9000 mutant proteins. Variant descriptions are provided on both hg19 and hg38 genome builds.
Mutation descriptions have been revised to better comply with HGVS nomenclature.
The dataset of germline mutations (germline variants in cancer patients/families) has been updated with data published between June 2018 and June 2019.
A new dataset including NGS studies reporting the frequency of individual TP53 germline mutations in case-control series is provided.
A large dataset on the functional impact of over 8200 p53 mutant proteins (Giacomelli et al., 2018) has been curated to add a new classification reflecting loss of function and dominant-negative effects (DNE_LOF class). A link to a website providing interactive access to these data is provided.
Four papers on funtional activities of mutant proteins have been curated.
Data on polymorphisms (variants frequent in healthy human populations) have been curated to include most recent data from dbSNP152 and gnomAD databases. Allelic frequencies have been retrieved from these databases to classify variants as "validated polymorphisms" if they are found at MAF>=0.001.
The dataset of somatic mutations is no longer updated as most new data are available in several other data portals (cBioportal, GENIE, COSMIC, ICGC). Instead, somatic mutation counts from TCGA, ICGC and GENIE datasets for each individual mutation is provided.
For data on TP53 status in cell-lines, a new link to the depmap resource has been created.
Mutation data from CLINVAR, June 2019 release, were curated.
Links to COSMIC, CLINVAR, gnomAD and dbSNP have been updated.
The dataset of induced mutations is unchanged as no new data were found.

This R19 release compiles data on over 29000 somatic mutations, 8000 variants reported in SNP databases, 1200 germline mutations related to Li-Fraumeni syndrome, 2700 cell-lines, 900 experimentally induced mutations, and functional data on over 4400 mutant proteins.
Variant descriptions are now provided on both hg19 and hg38 genome builds.
The dataset of germline mutations (rare disease-causing variants) has been updated with data published between January 2016 and June 2018. The dataset has increased by 30%!
The dataset of functional impact of p53 mutant proteins has been updated with 12 studies, including one major study that analyzed over 9500 DNA-binding domain variants for their growth suppression activity (see Kotler et al.,).
Data on polymorphisms (variants frequent in healthy human population) have been curated to include most recent data from dbSNP151, Flossie, gnomAD, 1000G and ESP6500 databases for the full TP53 gene sequence, including 5'UTR and 3'UTR regions (hg38, chr17:7661725-7689853). Allelic frequencies have been retrieved from these databases to classify variants as "validated polymorphisms" (MAF > 0.001 in at least one of these databases).
New annotations have been added on the predicted functional impact of variants by REVEL, BayesDel and an optimized Align-GVGD algorithm (see Fortuno et al.,).
Direct links to individual mutations in other databases have been added: CLINVAR, COSMIC, gnomAD.
The dataset of somatic mutations has not been updated as most new data are captured in other databases (cBioportal, COSMIC, TCGA and ICGC data portals). Instead we added somatic mutation counts from cBioportal for each individual mutation.
The dataset of induced mutations has not been changed because no new data were found.
Data on TP53 status in cell-lines have not been updated.

This R18 release compiles data on over 29,000 somatic mutations, 891 germline mutations, 2700 cell-lines, functional data on 2314 mutant proteins, and over 900 experimentally induced mutations (related to exposure to 17 different carcinogens).
The dataset of germline mutations (rare disease causing variants) has been updated with data published between 2013 and 2015.
The dataset of somatic mutations has been updated with one TCGA study on glioblastoma.
The dataset of induced mutations has been updated with 6 studies.
Data on polymorphisms (neutral variants frequent in healthy human population) in dbSNP, ESP and 1000G have been reviewed to update variant classification.
Data on TP53 status in cell-lines have been updated with recent CCLE data.
Variant descriptions are based on hg19 reference sequence but chromosome coordinates for genome builds hg18 and hg38 are also provided in downloaded files.
New annotations have been added: functional impact of variant predicted by Polyphen2, trinucleotide sequence context of variants.
The web interface has been updated to fix some issues with Jmol (Jmol was upgraded to JSmol to solve compatibility issues with some browsers) and to allow the input of list of mutations for querying all datasets. Some pages were also redesigned to improve navigation.

This R17 release compiles data on over 28,000 somatic mutations, 750 germline mutations, 2700 cell-lines, functional data on 2314 mutant proteins, and over 700 experimentally induced mutations (from exposure with 13 different carcinogens).
A new dataset on experimentally induced mutations has been added. It compiles mutations obtained in mutagenicity assays using the human TP53 gene (Hupki MEF and yeast assays).
The dataset of germline mutations has been updated with data published between November July 2012 and July 2013. Data on the prevalence of germline mutations have been fully integrated in the database scheme and made searchable on the web interactive search.
The dataset of somatic mutations has been updated with selected studies (ovarian cancer and adrenocortical carcinoma).
The dataset of functional impact of p53 mutant proteins has been updated with one study reporting DNE activity of 100 different mutants in a yeast assay (Monti et al., 2011).
The genome build hg19 is now used as default for describing mutations at the genome level.
The web interface has been updated to reflects the changes in database contents and annotations described above.

This R16 release compiles the occurence of 29575 somatic mutations, 635 germline mutations, functional data on 2314 mutant proteins and TP53 gene status of 2708 cell-lines.
The dataset of germline mutations has been updated with data published between November 2010 and July 2012.
The dataset of cell-lines has been updated with report published in 2010 and with data from the Cancer Cell Line Encyclopedia of the Broad Institute.
The datasets of functional impact of p53 mutant proteins and of somatic mutations (and associated Prognosis and Prevalence datasets) have been partially updated. For somatic mutations, data from recent large scale or whole genome sequencing studies have been curated (with the collaboration of COSMIC), as well as studies from IARC and data on rare cancers or cancers for which mutation data are not well represented in the database (such as upper urinary tract, kidney or head and neck cancers). Studies published between 2008 and 2011 have been included.
The web interface has been upgraded to ASP.NET for better functionalities and interactivities. New search options are available, including the full analysis of germline mutation dataset, the possibility to input a list of mutations, and to retrieve full annotations on functional/structural impacts of mutations and their frequency of occurence.

This R15 release contains 27580 somatic mutations, 597 germline mutations, functional data on 2314 mutant proteins and TP53 gene status of 2263 cell-lines.
The dataset of Somatic mutations (and associated Prognosis and Prevalence datasets) has been partially updated. Data from recent large scale or whole genome sequencing studies have been curated (with the collaboration of COSMIC) as well as data on liver and breast cancers published in 2008 and 2009.
The dataset of germline mutations has been updated with data published between September 2009 and October 2010.
The dataset of cell-lines has been updated with report published in 2008 and 2009 and with data from COSMIC Cell-line database. An extensive review of COSMIC data has been performed as we noticed that several cell_lines linked to Ref_ID 2056 (COSMIC database) were wrongly annotated as WT in previous releases. These entries were in fact cells not yet analyzed for TP53. This mistake has been corrected in the current version.
The datasets of functional activities of p53 mutant proteins and of mouse-models have not been updated.
A new set of data is available, the TP53_R249S dataset, that provides data on the prevalence of the p.R249S mutation in liver cancers. It includes studies that have screened exon 7 of TP53 by sequencing as well as studies that have searched for this specific mutation by RFLP. These data are also included in the Prevalence dataset. Data from studies that have anaylzed only codon 249 are no included in the Somatic dataset. The presence of this mutation in hepatocellular carcinomas has been linked to exposure to aflatoxins and HBV, and may thus constitutes a biomarker of exposure. This dataset can be downloaded from the Data download page.

Up to now, the IARC TP53 Database policy was to include all published papers reporting data on TP53 mutations, even if poor quality or artefactual data were suspected. The idea was to reflect literature data. However, due to increasing possible miss-use of the database (more non-specialists users), we decided to change the database policy.
Thus, starting with this R15 release of the database (November 2010), the following apply to the dataset of somatic mutations:
- New papers of poor quality have not been curated;
- Papers of poor quality previously included in the database are excluded from the online search results. These papers will remain available through the “Data download” option and will be identified by an annotation field called “Exclude analysis”. Twenty one papers (accounting for 972 mutations) have been identified as poor quality.
Poor data quality is suspected when:
- Several unusual mutations, especially silent or functional (based on transactivation assays) ones, are described;
- More than 3 mutations are found by sample;
- The same mutation is found in several samples of the same series, especially unusual mutations or silent or functional mutations;
- If the conditions above are in the context of studies that did not confirm mutations in independent PCR products and/or used nested PCR.

The dataset of somatic mutations has been updated with data reported in publications edited in PubMed in 2007 and the dataset of germline mutations has been updated with data reported in publications edited between August 2008 and August 2009. The datasets of functional activities of p53 mutant proteins and of mouse-models have not been updated. This R14 release contains 26597 somatic mutations, 535 germline mutations, functional data on 2314 mutant proteins and TP53 gene status of 1993 cell-lines.
New annotations have been generated on the predicted impact of mutations on the status of p53 protein isoforms (see details here). These annotations can be retrieved from the 'Mutation Validation' search option.
Statistics on the prevalence of TP53 germline mutations in selected cohorts has been added here.

A new reference sequence is used for TP53 gene. This sequence is based on the most recent version of the genome assembly. Its GenBank reference is NC_000017 (7512445..7531642). Sequences of the introns are more complete and acurate than in refseq X54156. The only change in exons is at the polymorphic site in codon 72, where a C is present in the new refseq, while a G was present in refseq X54156. Note that some mutations have been reannotated in light of the new sequence.
The database has been updated with data reported in publications edited in PubMed in 2007. All datasets have been updated except the dataset of somatic mutations. This R13 release contains 24785 somatic mutations, 423 germline mutations, functional data on 2314 mutant proteins and TP53 gene status of 1894 cell-lines.
New annotations on the predicted impact of mutations on splicing have been generated with available algorithms (see details here).
Information on polymorphism frequency has been added in the dataset of polymorphisms.
New annotations were introduced for the description of mutations to comply with HGVS standards.
All missense mutations reported in the IARC TP53 database have been submitted to SwissProt. Links between the two databases are thus now available.

The database has been updated with data reported in publications edited in PubMed in 2006. This R12 release contains 24810 somatic mutations, 399 germline mutations, functional data on 2314 mutant proteins and TP53 gene status of 1886 cell-lines.
A new dataset on mouse-models with engineered p53 has been added. There are 545 models listed in R12.
In the Function dataset 1, data on endogenous mutants have been added and an "assay design" has been assigned to each experiment to emphasize the quality of the data.
Data on protein stability of some mutants have been added.

The database has been updated with data reported in publications edited in PubMed in 2005. This R11 release contains 23544 somatic mutations, 376 germline mutations, functional data on 2314 mutant proteins and TP53 gene status of 1569 cell-lines.
The dataset on TP53 gene status in cell-lines has been greetly extended and a search tool has been developed to easily retrieve data.
The list of polymorphisms has been extended and updated with data from SNP databases, and links to other databases providing additional information on population frequency and disease associations have also been included.
A new classification for the transactivation capacity of mutant proteins has been generated from the original data by Kato et al. (2003)
New tools and information have been addded in the "TP53 resources" section, including a viewer of the genomic sequence of TP53 with exon-intron boundaries and highlighted polymorphic sites, and a list of p53 response-elements with their sequence and location.

Annotations on the functional impact (predicted or observed in experimental assays) of mutations have been added, as well as nucleotide substitution rates for each specific mutation. New interactive scatter plot graphs can be drawn to display this information.
The dataset on the transactivation activities of 2314 missense mutants on 8 p53-target genes generated by Kato et al. (2003) has been integrated in the database and can be downloaded with the mutation dataset.
A mutation validation tool has been implemented to check if a mutation is listed in the database and what is its functional impact.
A summary view of the properties of specific mutations can be obtained from the scatter plot graphs or from the mutation validation tool.
A search option has been added to analyze tumor spectrum associated with specific germline mutations.

The database has been updated with data reported in publications edited in PubMed in 2004. This R10 release contains 21,587 somatic mutations, 283 germline mutations and functional data on 426 mutant proteins.
All datasets can now be searched through SRS, a search system that allows to perform multiple user-defined queries and data retrieval in table or html formats.

The database has been updated with data reported in publications edited in PubMed between March 2003 and December 2003. This R9 release contains 19,809 somatic mutations, 264 germline mutations and functional data on 423 mutant proteins.
A tool has been developed to search and display data and annotations on the functional properties of mutants.
A tool has been developed to visualized the 3D structure of the DNA-binding domain of p53 and color specific codons.
A list of cell-lines for which the TP53 gene status is known can be downloaded as a tab-delimited text file.
The different datasets previously maintained separately in different MS Access databases have been integrated in one single relational database maintained in MS SQL server centered on the the gene variation module, allowing a better consistency in the description of mutations across datasets.
Duplicates/errors have been identified and removed from the somatic dataset (40 mutations).

The database has been updated with data reported in publications edited in PubMed between July 2002 and February 2003. This R8 release contains 18,585 somatic mutations, 225 germline mutations and functional data on 206 mutant proteins.
A new dataset has been created that provide annotations on the functional impact of mutations. It includes p53 mutants that have been tested in functional assays in yeast or human cells. This dataset can be downloaded as a tab-delimited text file.
Duplicates/errors have been identified and removed from the somatic dataset (28 mutations).

The database has been updated with data reported in publications edited in PubMed between July 2001 and June 2002. This R7 release contains 17,689 somatic mutations and 225 germline mutations.
A new dataset has been created that provides information on the prognostic value of TP53 gene mutations. It includes a list of studies that have investigated the prognostic value of TP53 gene mutation status in specific cancers. Study design and main findings are indicated. This dataset can be downloaded as a tab-delimited text file.
The dataset on the prevalence of TP53 gene mutations has been extended and made available as an Access file.
Duplicates/errors have been identified and removed from the somatic dataset (73 mutations).

The database has been updated with data reported in publications edited in PubMed between January 2001 and June 2001. This R6 release contains 16,285 somatic mutations, 213 germline mutations.
New annotations have been added to search individuals by population group, and mutations by genomic nucleotide position.
Duplicates have been identified and removed from the somatic dataset (385 mutations). Constant efforts are made to check for errors and track these duplicates. Despite these efforts, some may remain in the database and their identification is an ongoing task.

The database has been updated with data reported in publications edited in PubMed between May and December 2000. This R5 release contains 15,121 somatic mutations and 196 germline mutations.
A web application has been created to search and analyze the dataset of somatic mutations.
A new dataset has been created that provides data on the prevalence of TP53 gene mutations. Tumor site and sample numbers are indicated. This dataset can be downloaded as a tab-delimited text file.
A slide-show on TP53 mutations in human cancer is freely available as a downloadable ppt file.
Duplicates have been identified and removed from the somatic dataset (388 mutations). Constant efforts are made to check for errors and track these duplicates. Despite these efforts, some may remain in the database and their identification is an ongoing task.

The database has been updated with data reported in publications edited in PubMed between January 1998 and April 2000. This R4 release contains 14,000 somatic mutations and 144 germline mutations.
The datasets of somatic and germline mutations can be downloaded as tab-delimited text files.
A new database has been created in MS Access with a relational scheme to maintain data on germline TP53 mutations and Li-Fraumeni and Li-Fraumeni-Like syndromes.

IARC TP53 Database

Database developments