NGS Reveals Molecular Subgroups in Endometrioid Ovarian Carcinoma

The use of next-generation sequencing (NGS) demonstrated that the most prevalent genomic alterations in patients with endometrioid ovarian carcinoma include ARID1A, PIK3CA, PTEN, CTNNB1, KRAS, and P53, according to data from a study presented at the 2023 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.¹

Specifically, ARID1A mutations occurred in 39% of patient samples, and PIK3CA mutations had an incidence of 38%. The rates of PTEN, CTNNB1, KRAS, and P53 mutations were 37%, 36%, 28%, and 21%, respectively. These findings led investigators to conclude that endometrioid ovarian carcinoma has distinct molecular subgroups.

“We found a high incidence of ARID1A mutations [and] PIK3CA mutations, as well as PTEN, CTNNB1, KRAS, and P53 mutations,” lead study author, Dimitrios Nasioudis, MD, detailed in an interview with OncLive®. “What is interesting is the mutual exclusivity of P53 mutations with any of the other mutations, demonstrating that this is a distinct genomic subgroup of endometrial ovarian cancer.”

Nasioudis is a physician and a fellow of gynecologic oncology in the Department of Obstetrics and Gynecology at the University of Pennsylvania, Penn Medicine, in Philadelphia, Pennsylvania.

Because endometrioid ovarian carcinoma is a rare histological subtype of ovarian cancer, investigators sought to better understand the molecular profile of this disease through NGS.

“There is a need for novel treatment strategies for [endometrioid ovarian carcinoma]. Our aim was to investigate [patients’] unique molecular profile,” Nasioudis explained.

Investigators used the AACR Project Genie v13.0 genomic database to gather de-identified NGS data submitted from 18 institutions. Data from the OncoKB database provided by cBioPortal were used to determine the presence of pathogenic gene alterations.

Investigators collected a total of 267 samples from 260 patients, with 75.3% of samples originating from the primary tumor. The mean patient age at sample collection was 55.7 years (range, 23-88), and 72.1% of patients were White.

Additional genomic alteration observed included PIK3R1 (17%), CTCF (9%), KMT2D (7%), ARID1B (7%), ATM(6%), MSH6 (6%), APC (6%), NF1 (6%), CREBBP (5%), ATRX (4%), and BRCA2 (2%).

“The next steps will be to identify the subgroups’ association with survival, [which can help] guide the planning of molecular-driven trials in these subgroups,” Nasioudis said.

With the high incidence of MAPK/ERK and mTOR/PIK3CA pathway alterations, further investigation into the development of targeted therapeutics will be beneficial, Nasioudis and colleagues noted.

“[In] endometrioid ovarian cancer, although it’s a rare histologic subtype, there are actionable mutations,” Nasioudis concluded. “The use of NGS can identify patients [who] could benefit from enrollment in clinical trials or compassionate use of inhibitors.”

Reference

Nasioudis D, Gysler S, EM Ko, et al. Next generation sequencing reveals distinct molecular subgroups of endometrioid ovarian carcinoma. Presented at: 2023 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, Fl. Poster 1291