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A global analysis of the reconstitution of PTEN function by translational readthrough of PTEN pathogenic premature termination codons
Author(s) -
Luna Sandra,
Torices Leire,
Mingo Janire,
Amo Laura,
RodríguezEscudero Isabel,
RuizIbarlucea Pablo,
Erramuzpe Asier,
Cortés Jesús M.,
Tejada María I.,
Molina María,
NunesXavier Caroline E.,
López José I.,
Cid Víctor J.,
Pulido Rafael
Publication year - 2021
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.24186
Subject(s) - pten , biology , germline , genetics , gene , germline mutation , nonsense mutation , cancer research , suppressor , tumor suppressor gene , mutation , carcinogenesis , missense mutation , pi3k/akt/mtor pathway , apoptosis
The PTEN tumor suppressor gene is mutated with high incidence in tumors and in the germline of patients with cancer predisposition or with macrocephaly associated with autism. PTEN nonsense mutations generating premature termination codons (PTC) and producing nonfunctional truncated PTEN proteins are frequent in association with human disease. However, there are no studies addressing the restoration of full‐length PTEN proteins from the PTC‐mutated PTEN gene by translational readthrough. Here, we have performed a global translational and functional readthrough analysis of the complete collection of PTEN PTC somatic or hereditary mutations found in tumors or in the germline of patients (disease‐associated PTEN PTCome), and we set standards for the analysis of the potential of readthrough functional reconstitution in disease‐relevant genes. Our analysis indicates that prevalent pathogenic PTEN PTC mutations are susceptible to PTEN functional restoration in response to readthrough‐inducing compounds. Comprehensive readthrough analyses of disease‐associated PTComes will be valuable tools for the implementation of readthrough‐based precision interventions in specific groups of patients.