Identification of lung cancer drivers by comparison of the observed and the expected numbers of missense and nonsense mutations in individual human genes.
Catalog Of Somatic Mutations In Cancer (COSMIC)
driver genes
lung cancer
somatic mutations
Journal
Oncotarget
ISSN: 1949-2553
Titre abrégé: Oncotarget
Pays: United States
ID NLM: 101532965
Informations de publication
Date de publication:
2022
2022
Historique:
received:
13
03
2022
accepted:
03
05
2022
entrez:
31
5
2022
pubmed:
1
6
2022
medline:
1
6
2022
Statut:
epublish
Résumé
Largely, cancer development is driven by acquisition and positive selection of somatic mutations that increase proliferation and survival of tumor cells. As a result, genes related to cancer development tend to have an excess of somatic mutations in them. An excess of missense and/or nonsense mutations in a gene is an indicator of its cancer relevance. To identify genes with an excess of potentially functional missense or nonsense mutations one needs to compare the observed and expected numbers of mutations in the gene. We estimated the expected numbers of missense and nonsense mutations in individual human genes using (i) the number of potential sites for missense and nonsense mutations in individual transcripts and (ii) histology-specific nucleotide context-dependent mutation rates. To estimate mutation rates defined as the number of mutations per site per tumor we used silent mutations reported in the Catalog Of Somatic Mutations In Cancer (COSMIC). The estimates were nucleotide context dependent. We have identified 26 genes with an excess of missense and/or nonsense mutations for lung adenocarcinoma, 18 genes for small cell lung cancer, and 26 genes for squamous cell carcinoma of the lung. These genes include known genes and novel lung cancer gene candidates.
Identifiants
pubmed: 35634240
doi: 10.18632/oncotarget.28231
pii: 28231
pmc: PMC9132259
doi:
Substances chimiques
Codon, Nonsense
0
Nucleotides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Pagination
756-767Subventions
Organisme : NCI NIH HHS
ID : U19 CA203654
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA231141
Pays : United States
Organisme : NCI NIH HHS
ID : R03 CA256222
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA243483
Pays : United States
Organisme : NCI NIH HHS
ID : U19 CA148127
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA206980
Pays : United States
Informations de copyright
Copyright: © 2022 Gorlova et al.
Déclaration de conflit d'intérêts
CONFLICTS OF INTEREST The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
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