title: Meta-analysis of the p53 mutation database for mutant p53 biological activity reveals a methodologic bias in mutation detection.
abstract: OBJECTIVE
  Analyses of the pattern of p53 mutations have been essential for epidemiologic studies linking carcinogen exposure and cancer. We were concerned by the inclusion of dubious reports in the p53 databases that could lead to controversial analysis prejudicial to the scientific community.
  
  
  METHODS
  We used the universal mutation database p53 database (21,717 mutations) combined with a new p53 mutant activity database (2,300 mutants) to perform functional analysis of 1,992 publications reporting p53 alterations. This analysis was done using a statistical approach similar to that of clinical meta-analyses.
  
  
  RESULTS
  This analysis reveals that some reports of infrequent mutations are associated with almost normal activities of p53 proteins. These particular mutations are frequently found in studies reporting multiple mutations in one tumor, silent mutations, or lacking mutation hotspots. These reports are often associated with particular methodologies, such as nested PCR, for which key controls are not satisfactory.
  
  
  CONCLUSIONS
  We show the importance of accurate functional analysis before inferring any genetic variation. The quality of the p53 databases is essential in order to prevent erroneous analysis and/or conclusions. The availability of functional data from our new p53 web site (http://p53.free.fr and http://www.umd.be:2072/) will allow functional prescreening to identify potential artifactual data.
authors.affiliation: Laboratoire de Génotoxicologie des tumeurs, UPMC, Dpt Pneumologie, Hôpital Tenon, Paris, France. thierry.soussi@free.fr
authors.forename: Thierry
authors.initials: T
authors.lastname: Soussi
authors.forename: Bernard
authors.initials: B
authors.lastname: Asselain
authors.forename: Dalil
authors.initials: D
authors.lastname: Hamroun
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kato
authors.forename: Chikashi
authors.initials: C
authors.lastname: Ishioka
authors.forename: Mireille
authors.initials: M
authors.lastname: Claustres
authors.forename: Christophe
authors.initials: C
authors.lastname: Béroud
mesh_terms: D016208:Databases, Factual; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53