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Erschienen in: Endocrine 2/2022

18.05.2022 | Original Article

USP13 genetics and expression in a family with thyroid cancer

verfasst von: Andrea G. Maria, Bruna Azevedo, Nikolaos Settas, Fady Hannah-Shmouni, Constantine A. Stratakis, Fabio R. Faucz

Erschienen in: Endocrine | Ausgabe 2/2022

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Abstract

Purpose

Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma and its incidence has greatly increased in the last 30 years. Ubiquitin-specific protease 13 (USP13) is a class of deubiquitinating enzymes (DUBs) and plays an important role in cellular functions such as cell cycle regulation, DNA damage repair, and different cell signaling pathways. Studies regarding the role of USP13 in cancer development and progression are divergent and there are no previous data regarding the role of USP13 gene in PTCs. In this study, we investigated the genetic cause of PTC diagnosed in multiple members of a Brazilian family.

Methods

Whole exome sequencing (WES) was performed to identify the genetic cause of PTC. Cycloheximide chase assay and clonogenic assay were performed to study USP13 stability and function in vitro.

Results

WES analysis identified a heterozygous missense variant c.1483G > A (p.V495M) in the USP13 gene that fully segregates with the disease. In silico modeling suggests that this variant may cause protein structural perturbations. USP13 overexpression increased the potential of a single cell to form colonies. The USP13 c.1483G > A variant enhanced the effects seen in USP13 overexpression and preserved protein stability for longer hours compared to the non-mutated USP13 protein.

Conclusion

Our study suggests that USP13 overexpression may play a role in tumorigenesis of PTCs; and that the USP13 p.V495M (c.1483G > A) variant enhances USP13 estability.
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Metadaten
Titel
USP13 genetics and expression in a family with thyroid cancer
verfasst von
Andrea G. Maria
Bruna Azevedo
Nikolaos Settas
Fady Hannah-Shmouni
Constantine A. Stratakis
Fabio R. Faucz
Publikationsdatum
18.05.2022
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 2/2022
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-022-03068-x

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