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Updated: May 23, 2026

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

Correlation of DLC1 gene methylation with oncogenic PIK3CA mutations in extramammary Paget's disease

Zhihua Kang1, Feng Xu, Qiao-An Zhang

  • 1Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai, The People's Republic of China.

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
|April 24, 2012
PubMed

Insights

Aberrant methylation of the DLC1 gene and PIK3CA mutations are implicated in extramammary Paget

Area of Science:

  • Oncology
  • Dermatology
  • Molecular Biology
  • Epigenetics

Background:

  • Extramammary Paget's disease (EMPD) is a rare skin cancer with unknown genetic and epigenetic drivers.
  • Understanding the molecular basis of EMPD is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of the tumor suppressor gene DLC1 and the oncogene PIK3CA in EMPD pathogenesis.
  • To correlate genetic and epigenetic alterations with clinical pathology data in EMPD patients.

Main Methods:

  • Analysis of DLC1 expression, mutation, and methylation status in 132 EMPD tumors and 20 normal tissues.
  • Investigation of PIK3CA mutations in EMPD tumors using direct sequencing.
  • Correlation of molecular findings with patient pathology and clinical data.

Main Results:

  • DLC1 was downregulated in 33% of EMPD tumors.
  • DLC1 promoter hypermethylation was observed in 39% of tumors, correlating with decreased DLC1 levels and advanced age.
  • PIK3CA mutations were found in 24% of tumors, predominantly invasive types, and significantly correlated with DLC1 hypermethylation.

Conclusions:

  • Aberrant DLC1 methylation and PIK3CA mutations are potential key players in EMPD development and progression.
  • These molecular alterations may serve as promising therapeutic targets for extramammary Paget's disease.

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