Dysregulation of X chromosome inactivation in high grade ovarian serous adenocarcinoma

PloS One
Jun KangLee-so Maeng

Abstract

One of the two copies of the X chromosome is randomly inactivated in females as a means of dosage compensation. Loss of X chromosome inactivation (XCI) is observed in breast and ovarian cancers, and is frequent in basal-like subtype and BRCA1 mutation-associated breast cancers. We investigated the clinical implications of the loss of XCI in ovarian cancer and the association between the loss of XCI and BRCA1 dysfunction. We used open source data generated by The Cancer Genome Atlas (TCGA) Genome Data Analysis Centers. Ward's hierarchical clustering method was used to classify the methylation status of the X chromosome. We grouped 584 high grade serous ovarian adenocarcinomas (HG-SOA) according to methylation status, loss of heterozygosity and deletion or gain of X chromosome into the following five groups: preserved inactivated X chromosome (Xi) group (n = 175), partial reactivation of Xi group (n = 100), p arm deletion of Xi group (n = 35), q arm deletion of Xi group (n = 44), and two copies of active X group (n = 230). We found four genes (XAGE3, ZNF711, MAGEA4, and ZDHHC15) that were up-regulated by loss of XCI. HG-SOA with loss of XCI showed aggressive behavior (overall survival of partial reactivation of Xi group: HR 1.7, ...Continue Reading

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Citations

Sep 28, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Irene Cantone, Amanda G Fisher
Feb 13, 2020·Diagnostics·John Lewis EtterKevin H Eng

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Methods Mentioned

BETA
RNA-Seq

Software Mentioned

GSEA
CGDS
XIST
Integrative Genomics Viewer ( IGV )
R

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