Activating genomic alterations in the Gs alpha gene (GNAS) in 274 694 tumors.


Journal

Genes, chromosomes & cancer
ISSN: 1098-2264
Titre abrégé: Genes Chromosomes Cancer
Pays: United States
ID NLM: 9007329

Informations de publication

Date de publication:
09 2020
Historique:
received: 08 02 2020
revised: 16 04 2020
accepted: 20 04 2020
pubmed: 28 4 2020
medline: 7 7 2021
entrez: 28 4 2020
Statut: ppublish

Résumé

Activating point mutations in two codons (R201 and Q227) in the alpha subunit of the stimulatory GTP binding protein (GNAS) gene-coined gsp mutations-were originally reported in growth hormone secreting pituitary adenomas. In these tumor types, gsp activating mutations were associated with uncontrolled intracellular cAMP accumulation leading to cellular proliferation and tumor formation. Since the original description of gsp mutations in pituitary and later thyroid neoplasia, many more tumors were genotyped for these specific activating mutations. In this paradigm, GNAS is an oncogene that can be activated by other molecular mechanisms, such as DNA amplification and translocation. Herein, we describe the largest account to date of tumor types that harbor pathogenic GNAS genomic alterations (GAs) including the "classical" gsp activating point mutations, delineate some common features of these tumors, and speculate as to the possible mechanisms whereby GNAS activating GAs are associated with the various stages of tumorigenesis.

Identifiants

pubmed: 32337806
doi: 10.1002/gcc.22854
doi:

Substances chimiques

Chromogranins 0
GNAS protein, human EC 3.6.1.-
GTP-Binding Protein alpha Subunits, Gs EC 3.6.5.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

503-516

Informations de copyright

© 2020 Wiley Periodicals, Inc.

Références

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Auteurs

Amit Tirosh (A)

Endocrinology Institute, Tel-Aviv, Israel.
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Dexter X Jin (DX)

Cancer Genomics, Foundation Medicine, Inc, Cambridge, Massachusetts, USA.

Luiz De Marco (L)

Department of Surgery, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Yael Laitman (Y)

Oncogenetics Unit, Chaim Sheba Medical Center, Tel-Aviv, Israel.

Eitan Friedman (E)

Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Oncogenetics Unit, Chaim Sheba Medical Center, Tel-Aviv, Israel.

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