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Title: Single-hit inactivation drove tumor suppressor genes out of the X chromosome during evolution
Authors: Wang, Xiansong
Hu, Wei
Li, Xiangchun
Huang, Dan
Li, Qing
Chan, Hung
Zeng, Judeng
Xie, Chuan
Chen, Huarong
Liu, Xiaodong
Gin, Tony
Wang, Maggie Haitian
Cheng, Alfred Sze Lok
Kang, Wei
To, Ka-Fai
Plewczynski, Dariusz
Zhang, Qingpeng
Chen, Xiaoting
Chan, Danny Cheuk Wing
Ko, Ho
Wong, Sunny Hei
Yu, Jun
Chan, Matthew Tak Vai
Zhang, Lin
Wu, William Ka Kei
Keywords: Science::Medicine
Issue Date: 2022
Source: Wang, X., Hu, W., Li, X., Huang, D., Li, Q., Chan, H., Zeng, J., Xie, C., Chen, H., Liu, X., Gin, T., Wang, M. H., Cheng, A. S. L., Kang, W., To, K., Plewczynski, D., Zhang, Q., Chen, X., Chan, D. C. W., ...Wu, W. K. K. (2022). Single-hit inactivation drove tumor suppressor genes out of the X chromosome during evolution. Cancer Research, 82(8), 1482-1491.
Journal: Cancer Research
Abstract: Cancer-related genes are under intense evolutionary pressure. In this study, we conjecture that X-linked tumor suppressor genes (TSG) are not protected by the Knudson's two-hit mechanism and are therefore subject to negative selection. Accordingly, nearly all mammalian species exhibited lower TSG-to-noncancer gene ratios on their X chromosomes compared with nonmammalian species. Synteny analysis revealed that mammalian X-linked TSGs were depleted shortly after the emergence of the XY sex-determination system. A phylogeny-based model unveiled a higher X chromosome-to-autosome relocation flux for human TSGs. This was verified in other mammals by assessing the concordance/discordance of chromosomal locations of mammalian TSGs and their orthologs in Xenopus tropicalis. In humans, X-linked TSGs are younger or larger in size. Consistently, pan-cancer analysis revealed more frequent nonsynonymous somatic mutations of X-linked TSGs. These findings suggest that relocation of TSGs out of the X chromosome could confer a survival advantage by facilitating evasion of single-hit inactivation.
ISSN: 0008-5472
DOI: 10.1158/0008-5472.CAN-21-3458
Rights: © 2022 American Association for Cancer Research. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:LKCMedicine Journal Articles

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