人类肿瘤蛋白通过调节与细胞生长、增殖和死亡有关的信号通路，促进细胞向肿瘤的转化。尽管肿瘤蛋白在很多年前就已经被发现，并且已经在癌症的背景下得到了广泛的研究，但最近使用的高通量测序技术已可以鉴定其他条件下与癌症相关的突变，包括许多先天性疾病。由于其单基因性质，这些综合征为研究癌蛋白信号传导及其生物学提供了机会，而无需其他驱动或伴随突变。此外，它们在多个组织谱系中的表达在生理水平上，为原癌蛋白在转化组织和未受影响组织中的生物学研究提供了线索。鉴于最近关于癌蛋白如何促进转化的范式转变，我们回顾了癌蛋白双重性的遗传学，信号传导和发病机理的基础。

The duality of human oncoproteins: drivers of cancer and congenital disorders

Castel P, Rauen KA, McCormick F. The duality of human oncoproteins: drivers of cancer and congenital disorders. Nat Rev Cancer 2020.Pau Castel，Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA. E-mail: pau.castel@ucsf.edu.

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.