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The Duality of Human Oncoproteins: Drivers of Cancer and Congenital Disorders

Overview
Journal Nat Rev Cancer
Specialty Oncology
Date 2020 Apr 29
PMID 32341551
Citations 30
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Abstract

Human oncoproteins promote transformation of cells into tumours by dysregulating the signalling pathways that are involved in cell growth, proliferation and death. Although oncoproteins were discovered many years ago and have been widely studied in the context of cancer, the recent use of high-throughput sequencing techniques has led to the identification of cancer-associated mutations in other conditions, including many congenital disorders. These syndromes offer an opportunity to study oncoprotein signalling and its biology in the absence of additional driver or passenger mutations, as a result of their monogenic nature. Moreover, their expression in multiple tissue lineages provides insight into the biology of the proto-oncoprotein at the physiological level, in both transformed and unaffected tissues. Given the recent paradigm shift in regard to how oncoproteins promote transformation, we review the fundamentals of genetics, signalling and pathogenesis underlying oncoprotein duality.

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References
1.
Wang Y, Velho S, Vakiani E, Peng S, Bass A, Chu G . Mutant N-RAS protects colorectal cancer cells from stress-induced apoptosis and contributes to cancer development and progression. Cancer Discov. 2013; 3(3):294-307. PMC: 3595397. DOI: 10.1158/2159-8290.CD-12-0198. View

2.
Shirley M, Tang H, Gallione C, Baugher J, Frelin L, Cohen B . Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med. 2013; 368(21):1971-9. PMC: 3749068. DOI: 10.1056/NEJMoa1213507. View

3.
Huang J, Urtatiz O, Van Raamsdonk C . Oncogenic G Protein GNAQ Induces Uveal Melanoma and Intravasation in Mice. Cancer Res. 2015; 75(16):3384-97. DOI: 10.1158/0008-5472.CAN-14-3229. View

4.
Charbel C, Fontaine R, Malouf G, Picard A, Kadlub N, El-Murr N . NRAS mutation is the sole recurrent somatic mutation in large congenital melanocytic nevi. J Invest Dermatol. 2013; 134(4):1067-1074. DOI: 10.1038/jid.2013.429. View

5.
Tavormina P, Shiang R, Thompson L, Zhu Y, Wilkin D, Lachman R . Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3. Nat Genet. 1995; 9(3):321-8. DOI: 10.1038/ng0395-321. View