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Review
. 2018 Dec;16(12):1819-1825.
doi: 10.1158/1541-7786.MCR-18-0368. Epub 2018 Jul 23.

SWI/SNF Complexes in Ovarian Cancer: Mechanistic Insights and Therapeutic Implications

Takeshi Fukumoto  1 , Elizabeth Magno  1 , Rugang Zhang  2
Affiliations
Review

SWI/SNF Complexes in Ovarian Cancer: Mechanistic Insights and Therapeutic Implications

Takeshi Fukumoto et al. Mol Cancer Res. 2018 Dec.

Abstract

Ovarian cancer remains the most lethal gynecologic malignancy in the developed world. Despite the unprecedented progress in understanding the genetics of ovarian cancer, cures remain elusive due to a lack of insight into the mechanisms that can be targeted to develop new therapies. SWI/SNF chromatin remodeling complexes are genetically altered in approximately 20% of all human cancers. SWI/SNF alterations vary in different histologic subtypes of ovarian cancer, with ARID1A mutation occurring in approximately 50% of ovarian clear cell carcinomas. Given the complexity and prevalence of SWI/SNF alterations, ovarian cancer represents a paradigm for investigating the molecular basis and exploring therapeutic strategies for SWI/SNF alterations. This review discusses the recent progress in understanding SWI/SNF alterations in ovarian cancer and specifically focuses on: (i) ARID1A mutation in endometriosis-associated clear cell and endometrioid histologic subtypes of ovarian cancer; (ii) SMARCA4 mutation in small cell carcinoma of the ovary, hypercalcemic type; and (iii) amplification/upregulation of CARM1, a regulator of BAF155, in high-grade serous ovarian cancer. Understanding the molecular underpinning of SWI/SNF alterations in different histologic subtypes of ovarian cancer will provide mechanistic insight into how these alterations contribute to ovarian cancer. Finally, the review discusses how these newly gained insights can be leveraged to develop urgently needed therapeutic strategies in a personalized manner.

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Conflict of interest statement

Declaration of Interests: The authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.. SWI/SNF subunit alterations in different histological subtypes of ovarian cancer.
ARID1A mutation in endometriosis-associated ovarian clear cell and endometrioid cancer typically leads to loss of ARID1A protein expression. CARM1 amplification/upregulation in high-grade serous ovarian cancer (HGSOC) causes methylation of the SWI/SNF core subunit BAF155. SMARCA4 mutation and epigenetic silencing of SMARCA2 in small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), often result in the loss of both of the two mutually exclusive SWI/SNF catalytic ATPases, BRG1 or BRM.
See this image and copyright information in PMC

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