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. 2021 Mar 29;10(4):749.
doi: 10.3390/cells10040749.

Epithelial Cells of Deep Infiltrating Endometriosis Harbor Mutations in Cancer Driver Genes

Agnieszka Koppolu  1   2 , Radosław B Maksym  3 , Wiktor Paskal  4 , Marcin Machnicki  5 , Beata Rak  2   4   6 , Monika Pępek  2   5 , Filip Garbicz  2   4   6   7 , Kacper Pełka  4 , Zofia Kuśmierczyk  4 , Joanna Jacko  4 , Małgorzata Rydzanicz  1 , Magdalena Banach-Orłowska  6 , Tomasz Stokłosa  5 , Rafał Płoski  1 , Jacek Malejczyk  6   8 , Paweł K Włodarski  4
Affiliations

Epithelial Cells of Deep Infiltrating Endometriosis Harbor Mutations in Cancer Driver Genes

Agnieszka Koppolu et al. Cells. .

Abstract

Endometriosis is an inflammatory condition manifested by the presence of endometrial-like tissue outside of the uterine cavity. The most common clinical presentations of endometriosis are dysmenorrhea, infertility, and severe pelvic pain. Few hypotheses attempt to explain the pathogenesis of endometriosis; however, none of the theories have been fully confirmed or considered universal. We examined somatic mutations in eutopic endometrium samples, deep endometriotic nodules and peripheral blood from 13 women with deep endometriosis of the rectovaginal space. Somatic variants were identified in laser microdissected samples using next-generation sequencing. A custom panel of 1296 cancer-related genes was employed, and selected genes representing cancer drivers and non-drivers for endometrial and ovarian cancer were thoroughly investigated. All 59 detected somatic variants were of low mutated allele frequency (<10%). In deep ectopic lesions, detected variants were significantly more often located in cancer driver genes, whereas in eutopic endometrium, there was no such distribution. Our results converge with other reports, where cancer-related mutations were found in endometriosis without cancer, particularly recurrent KRAS mutations. Genetic alterations located in ectopic endometriotic nodules could contribute to their formation; nevertheless, to better understand the pathogenesis of this disease, more research in this area must be performed.

Keywords: NGS sequencing; deep endometriosis; endometrial glands; endometriosis; laser-capture microdissection; somatic variants.

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Conflict of interest statement

All authors declare no conflict of interest.

Figures

Figure 1
Figure 1
A single representative endometrial gland before (A) and after (B) laser microdissection from 8 µm tissue slice. For a demonstration of gland mapping, eosin and hematoxylin staining was used on this sample (on the left). For DNA extraction, sections were stained with hematoxylin only (on the right).
Figure 2
Figure 2
Number of cancer driver and non-driver mutations found in ectopic end eutopic tissues. Calculated using Fisher’s exact test.
See this image and copyright information in PMC

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