Cancer Driving Mutations in Endometriosis Lesions and Development of Progesterone Resistance

Tissues from 100 patients with endometriosis will be analyzed with droplet digital PCR (ddPCR) targeted sequencing and responders (n=50) will be compared to non-responders (n=50) after controlling confounding factors.

From a subset of the 100 cases, whole exome sequencing (WES) and Methylation-Specific PCR (MSP)-based methylation profiling on microdissected epithelium and stroma will be performed in matched eutopic and ectopic tissues from 20 patients with known cancer-associated mutations or 20 controls.

Primary outcomes

• Number of somatic cancer driver mutations in progesterone-resistant versus progesterone-sensitive endometriosis lesions. [Six month]: Whole exome sequencing will be used to identify somatic cancer-driver mutations with the presence of at least one of KRAS or ARID1A or PIK3CA or PPP2R1A cancer-driver mutations to assess any difference between progesterone-resistant endometriosis and progesterone-sensitive endometriosis.

Secondary outcomes

• Number of cancer driver mutations in eutopic versus ectopic endometrial tissue in control versus diseased subjects [Six month]: Whole exome sequencing in a subset of patients with progesterone-resistant disease and controls will be done using Twist exome 2.0 to assess the number of cancer driver mutations.
• Difference in DNA methylation PCR profile of endometriotic lesions in ectopic versus eutopic endometrium in control versus diseased subjects. [Six month]: DNA methylation profile of eutopic and ectopic endometrial tissue for a subset cases and controls will be done using Zymo-Seq Trio WGBS Library Kit (D5462) \& Methyl Direct kit (D5020) to assess for any difference.

Sex: Female, ages: 18 Years to 45 Years

Inclusion Criteria:

* Signed informed consent.
* Gender: female.
* Age: 18-45 years at the time of signing consent.
* Clinical or surgical diagnosis of endometriosis undergoing laparoscopy.
* Controls may not have clinical or surgical diagnosis of endometriosis.
* Regular menstrual cycles.
* BMI between 18-40 kg/m2.
* Sexually active or have had a previous vaginal exam that used a speculum.
* English speaking

Exclusion Criteria:

* Use of any kind of steroidal therapy including oral contraceptives, Norplant, estrogen replacement/supplemental therapy, androgens (Danazol, Cyclomen, Danocrine, testosterone) or progesterone. She may not be taking or be on Celebrex.
* Pregnant.
* Presence of pelvic infection.
* Mullerian anomalies with absence of a cervix.
* History of cancer of the reproductive tract.
* Presence of undiagnosed uterine bleeding.
* Treatment with intrauterine device (IUD) or progestin-containing intrauterine device.

• James Segars, MD, FACOG, Principal investigator, Professor

NIH grants: R01HD096147