Comprehensive assessment of TP53 loss of function using multiple combinatorial mutagenesis libraries.
Sci Rep
; 10(1): 20368, 2020 11 23.
Article
em En
| MEDLINE
| ID: mdl-33230179
ABSTRACT
The diagnosis of somatic and germline TP53 mutations in human tumors or in individuals prone to various types of cancer has now reached the clinic. To increase the accuracy of the prediction of TP53 variant pathogenicity, we gathered functional data from three independent large-scale saturation mutagenesis screening studies with experimental data for more than 10,000 TP53 variants performed in different settings (yeast or mammalian) and with different readouts (transcription, growth arrest or apoptosis). Correlation analysis and multidimensional scaling showed excellent agreement between all these variables. Furthermore, we found that some missense mutations localized in TP53 exons led to impaired TP53 splicing as shown by an analysis of the TP53 expression data from the cancer genome atlas. With the increasing availability of genomic, transcriptomic and proteomic data, it is essential to employ both protein and RNA prediction to accurately define variant pathogenicity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
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Biblioteca Gênica
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Proteína Supressora de Tumor p53
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Mutação
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Proteínas de Neoplasias
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Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
França