Mutation profile and chromosomal abnormality in adenomyosis

Area of Science:

• Gynecologic Oncology
• Genetics
• Molecular Biology

Background:

• Adenomyosis is a benign gynecologic condition characterized by the invasion of endometrial tissue into the uterine myometrium.
• The genetic underpinnings of adenomyosis development and progression remain incompletely understood.
• Identifying specific genomic alterations can provide insights into disease mechanisms and potential therapeutic targets.

Purpose of the Study:

• To identify distinct mutation profiles in adenomyotic epithelium compared to coexisting normal uterine endometrium.
• To investigate the clonal relationships and origins of adenomyosis using multi-regional tissue sampling.
• To analyze somatic copy number alterations (SCNAs) and mutational signatures in adenomyosis.

Main Methods:

• Tissue-selective next-generation sequencing (NGS) including target-gene and whole-exome sequencing.
• Laser microdissection for isolating pure epithelial and stromal samples from adenomyosis and endometrium.
• Multi-regional sampling from 21 patients with adenomyosis.

Main Results:

• Somatic mutations in cancer-associated genes (e.g., KRAS, PIK3CA, ARID1A) were identified in adenomyotic epithelium with high mutant allele frequencies.
• Recurring gain of chromosome 1q was observed in adenomyotic epithelium, but not in normal endometrium.
• Whole-exome sequencing demonstrated clonal relationships among multiple adenomyotic lesions and between adenomyosis and the normal endometrium, suggesting an oligoclonal origin.

Conclusions:

• Adenomyotic epithelium harbors specific genomic alterations, including mutations in cancer-associated genes and chromosomal gains, relevant to adenomyosis development.
• The study elucidates the oligoclonal origin of adenomyosis and the spatial expansion of mutated clones.
• These findings contribute to understanding the molecular pathogenesis of adenomyosis.