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. 2020 Feb 23;7(3):1690923.
doi: 10.1080/23723556.2019.1690923. eCollection 2020.

ARID1A mutation and genomic stability

Timothy Nacarelli  1 , Bo Zhao  1 , Xue Hao  1 , Rugang Zhang  1
Affiliations

ARID1A mutation and genomic stability

Timothy Nacarelli et al. Mol Cell Oncol. .

Abstract

We have recently discovered that AT-rich interactive domain-containing protein 1A (ARID1A) protects telomere cohesion through regulation of the cohesin subunit stromal antigen 1 (STAG1). ARID1A inactivation results in mitotic defects and negatively selects gross chromosomal aberrations, resulting in preservation of genomic stability in ARID1A-mutated cancers. These findings explain the long-standing paradox between mitotic defects caused by ARID1A inactivation and the lack of genomic instability in ARID1A-mutated cancers.

Keywords: ARID1A; OCCC; STAG1; SWI/SNF; genomic instability; mitotic defects; telomere.

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Figures

Figure 1.
Figure 1.
AT-rich interactive domain-containing protein 1A (ARID1A) inactivation selects against gross chromosomal aberrations and enriches for cancer cells with preserved genomic stability. ARID1A wildtype cells maintain telomere cohesion through stromal antigen 1 (STAG1) expression and undergo normal mitosis. However, ARID1A-inactivated cells exhibit defects in telomere cohesion through reduced STAG1 expression. Consequently, ARID1A-inactivated cells develop gross chromosomal aberrations and mitotic defects that lead to cell death. While this cell population is negatively selected, a separate surviving cell population is enriched that exhibits preserved genomic stability and decreased sensitivity to paclitaxel (PTX).
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