DATABASES ARTICLE The IARC TP53 Database: New Online Mutation Analysis and Recommendations to Users Magali Olivier, 1 Ros Eeles, 2 Monica Hollstein, 3 Mohammed A. Khan, 4 Curtis C. Harris, 4 and Pierre Hainaut 1 * 1 Molecular Carcinogenesis Group, International Agency for Research on Cancer, World Health Organization, Lyon, France 2 Cancer Genetics Team, Institute of Cancer Research, Sutton, Surrey, UK 3 German Cancer Research Center, Heidelberg, Germany 4 Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Communicated by Richard G.H. Cotton Mutations in the tumor suppressor gene TP53 are frequent in most human cancers. Comparison of the mutation patterns in different cancers may reveal clues on the natural history of the disease. Over the past 10 years, several databases of TP53 mutations have been developed. The most extensive of these databases is maintained and developed at the International Agency for Research on Cancer. The database compiles all mutations (somatic and inherited), as well as polymor- phisms, that have been reported in the published literature since 1989. The IARC TP53 mutation dataset is the largest dataset available on the variations of any human gene. The database is avail- able at www.iarc.fr/P53/. In this paper, we describe recent developments of the database. These developments include restructuring of the database, which is now patient-centered, with more detailed annotations on the patient (carcinogen exposure, virus infection, genetic background). In addition, a new on-line application to retrieve somatic mutation data and analyze mutation pat- terns is now available. We also discuss limitations on the use of the database and provide recom- mendations to users. Hum Mutat 19:607614, 2002. © 2002 Wiley-Liss, Inc. KEY WORDS: TP53; p53; mutation analysis; database; Li-Fraumeni syndrome; LFS; cancer; tumor sup- pressor DATABASES: TP53  OMIM: 191170, 151623 (LFS); GDB: 120445; GenBank: X54156; www.iarc.fr/P53 (The IARC TP53 Database) The tumor suppressor gene TP53 (MIM# 191117) encodes a transcription factor with multiple, anti-proliferative functions activated in response to several forms of cellular stress. Somatic TP53 gene alterations are frequent in most human cancers and inherited TP53 muta- tions predispose to a wide spectrum of early-on- set cancers (e.g., Li-Fraumeni Syndrome, LFS; MIM# 151623). Most TP53 mutations abrogate p53 transcriptional activity and result in the loss of its anti-proliferative properties [Hainaut and Hollstein, 2000]. Some TP53 mutations result in gain of oncogenic functions including attenu- ating the function of the p73 gene [Strano et al., 2000]. The types of mutations observed in the germline and in sporadic cancer cases are simi- lar, with a high prevalence of missense mutations (>75%). Thus, TP53 differs from other tumor suppressor genes such as RB1, APC, or BRCA1, which are frequently inactivated by deletions, frameshift mutations, or nonsense mutations. Received 11 November 2001; accepted revised manuscript 5 February 2002. *Correspondence to: Pierre Hainaut, Molecular Carcinogen- esis Group, International Agency for Research on Cancer, World Health Organization, 150 Cours Albert Thomas, 69372 Lyon cedex 08, France. E-mail: Hainaut@iarc.fr Contract grant sponsor: IARC; Contract grant sponsor: BIOMED program of the European Community; Contract grant number: QLG-1999-00273. DOI: 10.1002/humu.10081 Published online in Wiley InterScience (www.interscience.wiley. com).