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Updated: Oct 2, 2025

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
07:50

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer

Published on: September 18, 2020

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Cellular context determines DNA methylation profiles in SWI/SNF-deficient cancers of the gynecologic tract

Felix Kf Kommoss1, Basile Tessier-Cloutier2, Leora Witkowski3,4,5

  • 1Department of Pathology, Heidelberg University Hospital, Heidelberg, Germany.

The Journal of Pathology
|February 26, 2022
PubMed

Insights

SWI/SNF complex deficiency in gynecologic cancers presents diagnostic challenges. Distinct DNA methylation signatures reveal cellular context influences epigenetics, aiding diagnosis of undifferentiated cancers.

Area of Science:

  • Oncology
  • Genetics
  • Epigenetics

Background:

  • SWI/SNF (SWItch/Sucrose Non-Fermentable) complex deficiency is linked to undifferentiated cancers.
  • SWI/SNF-deficient gynecologic cancers are diagnostically challenging with unknown cellular origins.

Purpose of the Study:

  • To investigate the cellular origins and diagnostic markers of SWI/SNF-deficient gynecologic cancers.
  • To differentiate between undifferentiated endometrial carcinoma (UDEC), SMARCA4-deficient uterine sarcoma (SDUS), and ovarian small cell carcinoma, hypercalcemic type (SCCOHT).

Main Methods:

  • DNA methylation profiling of UDEC, SDUS, and SCCOHT.
  • Copy number analyses and differential methylation analyses.
  • Comparison with endometrioid endometrial carcinomas and extracranial malignant rhabdoid tumors.

Main Results:

  • UDEC, SDUS, and SCCOHT exhibit distinct DNA methylation signatures despite shared SWI/SNF inactivation and morphology.
  • Cellular context significantly impacts the epigenetic landscape in SWI/SNF-deficient cancers.
  • SDUS and SCCOHT share analogous molecular features, suggesting they are chromosomally stable SWI/SNF-deficient cancers within the malignant rhabdoid tumor spectrum.

Conclusions:

  • DNA methylation profiling is a valuable diagnostic tool for undifferentiated, SWI/SNF-deficient gynecologic cancers.
  • SDUS and SCCOHT are molecularly related and represent a subset of gynecologic SWI/SNF-deficient tumors.
  • Understanding epigenetic landscapes in SWI/SNF-deficient cancers is crucial for accurate diagnosis and classification.
Keywords:
ARID1BDNA methylationSMARCA4SMARCA4-deficient uterine sarcomaSMARCB1SWI/SNF deficiencygynecologic tractsmall cell carcinoma hypercalcemic typeundifferentiated endometrial carcinoma

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