p53 database

Download the database

On line guide

Database curation

MUT-MAT 2: p53 mutation prediction

p53 mutation in cell lines
(new)

p53 mutation and cancers: an extensive analysis of p53 mutation in every cancer

The p53 Mutation Handbook

p53 mutation distribution

p53 mutation in breast cancer: about apples, oranges and unusual p53 mutations:
a response to Patoc et al.

Documentation of the UMD p53 mutation database, Release 2010_R1

Analysis and description of this recent release of the UMD p53 mutation database can be found here:

Hamroun D, Kato S, Ishioka C, Claustres M, Beroud C, Soussi T (2006) The UMD TP53 database and website: update and revisions. Hum Mutat 27: 14-20.
Soussi T, Ishioka C, Claustres M, Beroud C (2006) Locus-specific mutation databases: pitfalls and good practice based on the p53 experience. Nat Rev Cancer 6: 83-90.

Problems and bias associated with the publication of p53 mutations have been fully described.

Soussi T, Beroud C (2001) Assessing TP53 status in human tumors to evaluate clinical outcome. Nat Rev Cancer 1: 233-240.
Soussi T, Beroud C (2003) Significance of TP53 mutations in human cancer: a critical analysis of mutations at CpG dinucleotides. Hum Mutat 21: 192-200.
Soussi T, Asselain B, Hamroun D, Kato S, Ishioka C, Claustres M, Beroud C (2006) Meta-analysis of the p53 mutation database for mutant p53 biological activity reveals a methodologic bias in mutation detection. Clin Cancer Res 12: 62-69.

Description of the UMD p53 database

Each row in the table represents a single mutation arbitrarily assigned with a unique identification number.
Files have been sorted by reference number

File #	Unique identification number for this mutation
Mutation position	Nucleotide position using the p53 cDNA as a reference (1 is the A of the start ATG)
Codon	Codon position (1 to 393)
Exon	Exon
	Mutations/variations in intron are not included in the UMD p53 database as the majority of them have not been associated with splicing defects.
WT codon	Normal base sequence of the codon in which the mutation occurred
Mutant codon	Sequence of the mutated codon. If the mutation is a deletion or an insertion, it is indicated by "del" or "ins" followed by the number of deleted or inserted bases. The position in the codon is indicated by “a”, “b”, or “c” for the first, second or third base of the codon respectively. Example: "del66b" is a deletion of 66 bases including the second base of the codon; "ins4a" is an insertion of 4 bases occurring between the first and the second base of the codon. Label a, b, or c is omitted if the boundary of the deletion or insertion is unknown.
WT AA	Wild type amino acid
Mutant AA	Mutant amino acid. Stop: nonsense mutation: Fs.: Frameshift mutation: InF: In-frame insertion or deletion
Name	Name of the tumor/patient/cell line as given by the authors. If the publication does not include any sample name, we have arbitrarily assigned a name, usually the first letters of the last author's name, followed by the numbers in the series. The same name or number can occur several times in a single study as in some samples more than one mutation has been reported (see complexity to find samples with multiple mutations). For cell lines, we used the name given in the publication. Unfortunately, there is some confusion as similar cell lines can appear with multiple names (acronym or ATCC references, change/errors in the acronym). Care has been taken to ensure some homogeneity
Variation type	Mutation: the nucleotide variation is associated with a change of the amino-acid: Polymorphism: the nucleotide variation is not associated with a change in the amino-acid sequence.
	Exonic mutations that do not changed amino acid sequences are not always neutral. The p53 mutation at codon 125 (ACG->ACA, T125T) was described by many authors as a polymorphic variant. RNA analysis of this mutation, located at the 3’ extremity of exon 4, shows that the splicing of the p53 gene is totally aberrant (Warneford et al., 1992)
Event	Mutational event: G>C: (G to C base change); C->A/C->T: complex mutation that change two nucleotide in the codon (C to A and C to T base change); Stop at 344: frameshift mutation leading to a premature stop codon and the synthesis of a truncated protein of 344 residues; In frame del or In frame Ins: deletion/insertion of that do not change the open reading frame of the p53 protein.
Type	Ts: Transition (a pyrimidine (C or T) is substituted by another pyrimidine, or a purine (A or G) is substituted by another purine); Tv: Transversion (a transversion mutation involves the change from a pyrimidine to a purine, or vice versa); Fr: Frameshift mutations (deletion / insertion); Ts/Ts: for mutation that target two nucleotides in the same codon; InF: deletion/insertion of that do not change the open reading frame of the p53 protein.
Complexity	SM: Single mutational event in the tumor; DMU (Double Mutation Unknown): Two p53 mutations in the same tumor but their allelique distribution is unknown; DMD (Double Mutation Different allele): Two p53 mutations in the same tumor on two different p53 allele; DMD (Double Mutation Same allele): Two p53 mutations in the same tumor on the same p53 allele: MM (Multiple Mutation): More than two p53 mutations in the same tumor.
Mutation type	B: single missense mutation; F: single nucleotide insertion or deletion; D: Deletion (2 or more nucleotides); I: insertion (2 or mores nucleotides); T: tandem mutation
CpG	Yes: transition (G to A or C to T base change) at a CpG dinucleotide; No: transitions (G to A or C to T base change) at non CpG Sites and all transversion
Py-Py doublets	Indicates whether or not a mutation target a Py-Py doublet Py-Py doublet: two adjacent pyrimidine residues (cytosine or thymine) that can be targeted by UV light. Yes, non coding strand: mutation localized at a Py-Py doublets on the non coding strand of the p53 gene; Yes, coding strand: mutation localized at a Py-Py doublets on the coding strand of the p53 gene; No: mutation localized outside a Py-Py doublet
Structure	Post-translational modifications of the codon: phosphorylation (Ser or Thr); ubiquitination; neddylation; methylation; acetylation
HCD	HCD I to V: Highly Conserved Domain I to V; DNA Binding: DNA binding domain: Negative regulation: carboxy-terminus of the p53 protein associated with a negative regulation of for p53 DNA binding activity; Transactivation: transactivation domain of the p53 protein; Proline Rich: Proline rich domain of the p53 protein; NES: Nuclear export signal of p53; NLS: Nuclear localization signal of p53; oligomerization: Tetramerization domain of the p53 protein.
Origin	Origin of the sample with the p53 mutations; Tumor: tumor tissue (biopsy, surgical specimen, cytology specimen) from cancer patients; Cell line: self explanatory; For cell lines, when the status of the original tumor is also known, a second entry with the same name but labeled as « tumor » is included in the database; Germline: constitutional p53 mutation associated with familial cancer such as Li-Fraumeni syndrome (LFS), Li-Fraumeni like syndrome (LFSL).
Cancer	Cancer name
Genetic background	Tumors can occur in patients with particular syndromes or with known germline mutations in other tumor suppressor genes or after. BRCA1: patients with a germline mutation in the BRCA1 gene BRCA2: patients with a germline mutation in the BRCA2 gene XP-C: Xeroderma Pigmentosum type C XP-D: Xeroderma Pigmentosum type D XP-E: Xeroderma Pigmentosum type E XP-V: Xeroderma Pigmentosum variant PTEN: patients with a germline mutation in the Phosphatase and TENsin homolog gene associated with a Cowden disease CHK2: patients with a germline mutation in the checkpoint kinase 2 gene associated with a Li-Fraumeni syndrome FA-C: Fanconi anemia type C Familial Breast cancer: familial cancer with no mutation identified PTCH: patients with a germline mutation in the patched gene P152L gl mutation: Patients with a p53 germline mutation at codon 152 and prone for adrenocortical tumors with several secondary p53 mutations in their tumors. NF1: patients with a germline mutation in the NF1 gene RDEB: patients with recessive dystrophic epidermolysis bullosa HNPCC: hereditary non polyposis colon cancer
Tumor type	Solid: Non hematological tumor Leu: all leukemia and lymphoma
Tumor site	Int.: all internal tumors Skin: all skin tumors
Smoking status	Information on the smoking status of the patient Yes, No, Unknown or Ex smoker
Aflatoxin status	Exposition of the patient to Aflatoxin B1: Yes, No or Unknown
Radiations	Exposition of the patient to radiation: Yes, No or Unknown
Drinking status	Information on the drinking status of the patient Yes, No or Unknown
Asbestos	Exposition of the patient to Asbestos: Yes, No or Unknown
Hepatitis B	Detection of HBV in the tumor; Yes, No or Unknown
Papilloma	Detection of HPV in the tumor; Yes, No or Unknown
Pro72 Const	Germline genotype at codon 72 (exon 4): Arg/Arg, Arg/Po or Pro/Pro
Pro72 Tum	Genotype of codon 72 associated with the p53 mutant: Arg or Pro.
Number of records	Number of tumors with this particular mutant the database
Ref#	Reference identification number
Authors	Authors
Year	Year
Title	Title
Journal	Journal
Volume	Volume
Page(s)	Page(s)
Medline	Medline
Mutant activities (mutant)	Data on AQ to AX columns are taken from the work of Kato et al.,( Kato S, Han SY, Liu W, Otsuka K, Shibata H, Kanamaru R, Ishioka C (2003) Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis. Proc Natl Acad Sci U S A 100: 8424-8429). Transactivation was tested using a yeast assay. The residual transcriptional activity of mutant p53 is always compared to wild type p53 for the same promoter (%). Wt: mutation that does not change the amino acid: Be aware that some of these mutation can change splicing or RNA stability Fr: Frameshift mutations. No activity data is available but it is usually assumed that no p53 is produced Tr: Terminating mutation: No activity data is available but it is usually assumed that no p53 is produced ND: No data available for this mutant
WAF1	Residual transcriptional activity of mutant p53 on the WAF1 promoter (% compared to wild type p53).
MDM2	Residual transcriptional activity of mutant p53 on the MDM2 promoter (% compared to wild type p53).
BAX	Residual transcriptional activity of mutant p53 on the BAX promoter (% compared to wild type p53).
14_3_3_sigma	Residual transcriptional activity of mutant p53 on the 14-3-3-s promoter (% compared to wild type p53).
AIP	Residual transcriptional activity of mutant p53 on the AIP promoter (% compared to wild type p53).
GADD45	Residual transcriptional activity of mutant p53 on the GADD45 promoter (% compared to wild type p53).
NOXA	Residual transcriptional activity of mutant p53 on the NOXA promoter (% compared to wild type p53).
p53R2	Residual transcriptional activity of mutant p53 on the p52R2 promoter (% compared to wild type p53).
Mutant Name	Mutant names using the official nomenclature as define by Antonorakis et al. (den Dunnen JT & Antonorakis SE. Mutation nomenclature extensions and suggestions to describe complex mutations: A discussion. Hum Mutat 2000; 15: 7-12)
Comments	Self-explanatory
Cut-Off	Out of range studies using either 95 ou 99% as a cut-off

____________________________________________________________________________________

The UMD p53 database is protected by the European Union Council Directive N° 96/9/EC, OJ (L77) 20 (1996). Extracting, copying or reuse of data from databases without permission are covered by this directive