Genomic alterations in ovarian endometriosis and subsequently diagnosed ovarian carcinoma

A Linder ¹, S Westbom-Fremer ^2,3, C Mateoiu ⁴

⁰Department of Obstetrics and Gynecology, Sahlgrenska Center for Cancer Research, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

Human Reproduction (Oxford, England) +

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March 9, 2024

View abstract on PubMed

Summary

Genetic analysis suggests ovarian cancer does not arise from endometriosis with cancer-like mutations, but a common precursor is likely. Early genetic alterations in immune response genes are significant in this process.

Area Of Science

Gynecologic Oncology
Cancer Genetics
Molecular Pathology

Background

Epidemiologic studies and shared mutations suggest endometriosis may precede ovarian carcinoma.
Endometrioid and clear cell ovarian carcinomas are the most common endometriosis-associated types (EAOCs).

Purpose Of The Study

To investigate the alleged association between ovarian endometriosis and ovarian carcinoma using genetic analysis.
To determine if endometriosis diagnosed before carcinoma shares cancer-like genetic profiles.

Main Methods

Whole-exome sequencing of DNA from 11 paired endometriosis and ovarian carcinoma samples.
Analysis of somatic variants, mutational signatures, microsatellite instability, and mismatch repair status.
Comparison of genetic profiles between pre-cancerous endometriosis and subsequent carcinoma.

Main Results

All paired samples showed shared somatic mutations, supporting a common cellular origin.
Cancer-associated mutations in endometriosis were not found in subsequent carcinomas.
Mutations in immune escape genes were conserved, and copy number alterations were frequent.

Conclusions

Ovarian carcinoma likely does not originate from endometriosis with identical cancer-like genetic profiles.
A common precursor for both conditions is probable.
Genetic alterations in immune response pathways appear to be early and significant events.

Keywords:

clear cell ovarian carcinoma copy number alteration endometrioid ovarian carcinoma exome-sequencing mutation ovarian endometriosis

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