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Predicting the oncogenicity of missense mutations reported in the International Agency for Cancer Research (IARC) mutation database on p53
Author(s) -
Gorlov Ivan P.,
Gorlova Olga Y.,
Amos Christopher I.
Publication year - 2005
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20242
Subject(s) - missense mutation , nonsense mutation , genetics , biology , mutation , nonsense , gene , database , computer science
Many mutation databases, comprising thousands of reported mutations, are available. Often the clinical significance of the reported mutations is unknown. In this study we developed an algorithm that allows prediction of the clinical significance of missense mutations reported in a mutation database. Nonsense mutations are used as a referent group for this assessment. We used the International Association for Research on Cancer (IARC) mutation database on TP53 to implement the algorithm. First, on the basis of published data [Nachman MW, Crowell SL. 2000. Genetics 156:297–304], we ascribed mutation rates to every single nucleotide substitution (SNS) in the core domain of the TP53 gene. Second, for every possible SNS we computed the expected number of missense mutations, under the assumption that missense mutations are as oncogenic as nonsense ones. The natural logarithm of the ratio of the observed to the expected number of missense mutations (LR) was used as a quantitative measure of oncogenicity (i.e., the ability of a mutation to produce cancer). We estimated the relative oncogenicity of all missense mutations reported in the IARC p53 mutation database, and constructed a profile of oncogenicity of the missense mutations along the DNA‐binding region of p53. Hum Mutat 26(5), 446–454, 2005. © 2005 Wiley‐Liss, Inc.