SWI/SNF Complex Mutations in Gynecologic Cancers: Molecular Mechanisms and Models

Annu Rev Pathol. 2020 Jan 24:15:467-492. doi: 10.1146/annurev-pathmechdis-012418-012917.

Abstract

The SWI/SNF (mating type SWItch/Sucrose NonFermentable) chromatin remodeling complexes interact with histones and transcription factors to modulate chromatin structure and control gene expression. These evolutionarily conserved multisubunit protein complexes are involved in regulating many biological functions, such as differentiation and cell proliferation. Genomic studies have revealed frequent mutations of genes encoding multiple subunits of the SWI/SNF complexes in a wide spectrum of cancer types, including gynecologic cancers. These SWI/SNF mutations occur at different stages of tumor development and are restricted to unique histologic types of gynecologic cancers. Thus, SWI/SNF mutations have to function in the appropriate tissue and cell context to promote gynecologic cancer initiation and progression. In this review, we summarize the current knowledge of SWI/SNF mutations in the development of gynecologic cancers to provide insights into both molecular pathogenesis and possible treatment implications for these diseases.

Keywords: ARID1A; DDEC; SCCOHT; SMARCA4; SWI/SNF; clear cell carcinoma of the ovary; dedifferentiated endometrial carcinoma; small cell carcinoma of the ovary hypercalcemic type.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chromosomal Proteins, Non-Histone / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genital Neoplasms, Female / genetics*
  • Genital Neoplasms, Female / therapy
  • Humans
  • Models, Genetic
  • Mutation*
  • Signal Transduction / genetics
  • Transcription Factors / genetics*

Substances

  • Chromosomal Proteins, Non-Histone
  • SWI-SNF-B chromatin-remodeling complex
  • Transcription Factors