Somatic XIST activation and features of X chromosome inactivation in male human cancers

Ananthan Sadagopan; Imran T Nasim; Jiao Li; Mingkee Achom; Cheng-Zhong Zhang; Srinivas R Viswanathan

doi:10.1016/j.cels.2022.10.002

Somatic XIST activation and features of X chromosome inactivation in male human cancers

Cell Syst. 2022 Nov 16;13(11):932-944.e5. doi: 10.1016/j.cels.2022.10.002. Epub 2022 Nov 9.

Authors

Ananthan Sadagopan¹, Imran T Nasim², Jiao Li¹, Mingkee Achom¹, Cheng-Zhong Zhang³, Srinivas R Viswanathan⁴

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
² Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.
³ Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Biomedical Informatics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: cheng-zhong_zhang@dfci.harvard.edu.
⁴ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: srinivas.viswanathan@dfci.harvard.edu.

PMID: 36356577
DOI: 10.1016/j.cels.2022.10.002

Abstract

Expression of the non-coding RNA XIST is essential for initiating X chromosome inactivation (XCI) during early development in female mammals. As the main function of XCI is to enable dosage compensation of chromosome X genes between the sexes, XCI and XIST expression are generally absent in male normal tissues, except in germ cells and in individuals with supernumerary X chromosomes. Via a systematic analysis of public sequencing data of both cancerous and normal tissues, we report that XIST is somatically activated in a subset of male human cancers across diverse lineages. Some of these cancers display hallmarks of XCI, including silencing of gene expression, reduced chromatin accessibility, and increased DNA methylation across chromosome X, suggesting that the developmentally restricted, female-specific program of XCI can be somatically accessed in male cancers.

Keywords: X chromosome inactivation; XIST; aneuploidy; cancer; germ tumors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Dosage Compensation, Genetic
Female
Humans
Male
Mammals / genetics
Neoplasms* / genetics
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
X Chromosome / metabolism
X Chromosome Inactivation / genetics

Substances

RNA, Long Noncoding