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Related Experiment Video

Updated: Jan 23, 2026

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Oncogenic mutations in histologically normal endometrium: the new normal?

Vivian Lac1, Tayyebeh M Nazeran1,2, Basile Tessier-Cloutier3

  • 1Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, BC, Canada.

The Journal of Pathology
|June 13, 2019
PubMed
Summary

Somatic driver mutations, common in cancer, were found in over 50% of normal endometrial tissues. These mutations, including KRAS and PIK3CA, increase with age, impacting our understanding of aging and cancer detection.

Keywords:
agingdigital PCRendometriumnormal tissuesomatic mutations

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Area of Science:

  • Oncology
  • Genetics
  • Pathology

Background:

  • Next-generation sequencing reveals somatic driver mutations in normal tissues, including skin, blood, and esophagus.
  • Endometrial tissue's regenerative nature and prior findings in endometriosis suggest potential for mutations.
  • Previous research by our group and others identified recurrent somatic driver mutations in endometriosis tissues.

Purpose of the Study:

  • To investigate the presence of somatic driver mutations in histologically normal endometrial tissue.
  • To determine if mutations like KRAS, PIK3CA, and FGFR2 exist in non-cancerous endometrium.
  • To assess the correlation between age and the prevalence of these mutations in normal endometrial tissue.

Main Methods:

  • Targeted sequencing of formalin-fixed, paraffin-embedded endometrial specimens from 110 women.
  • Orthogonal validation using droplet digital PCR for detected mutations.
  • Immunohistochemistry for PTEN and ARID1A as surrogates for gene inactivation.

Main Results:

  • Over 50% of normal endometrial samples exhibited somatic driver-like events.
  • Hotspot mutations in KRAS, PIK3CA, and FGFR2 were identified.
  • PTEN loss by immunohistochemistry was observed, and mutation prevalence increased with age (OR: 1.05).

Conclusions:

  • Somatic driver mutations are prevalent in histologically normal endometrium.
  • These findings challenge the concept of 'normal' tissue and have implications for early cancer detection tools.
  • The presence of mutations in normal tissues necessitates caution in interpreting results from mutation-based screening methods.