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Exome + targeted sequencing of ovarian endometriosis
(Suda et al, Cell Reports 2018)
• ‘Discovery’ whole exome sequencing of epithelium dissected through laser capture, from: – 13 ovarian endometriosis vs. 11 histologically normal eutopic endometrium samples
• Additional targeted (84 genes) sequencing of epithelium from:
– 94 ovarian endometriosis from 45 women vs.
– 71 eutopic endometrium from 29 women with ‘benign gynaecological disease’ (endometriosis, uterine fibroids, CIN)
Results:
• KRAS, PIK3CA most frequently mutated
• Evidence for clonal expansion from eutopic endometrium to endometriosis
• Bilateral endometrioma showed distinct mutational patterns: independent
• Mutations in cancer-associated genes present in many ‘normal’ tissues: explore ‘resilience factors’ that protect against their effects?
Conclusions
• There is no single ‘gene for endometriosis’... more complex
• Stage III/IV is different in genetic heritable origin from stage I/II
(what does that mean?? Further subtype identification needed)
• Increased somatic genetic variation in endometriosis – role in pathogenesis unclear
• Functional studies in relevant tissues are required to understand the impact of genetic variants on biology and pathogenesis - transcriptomics and epigenomics
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