Details

Autor(en) / Beteiligte

• Praiss, Aaron M.
• Marra, Antonio
• Zhou, Qin
• Rios-Doria, Eric
• Momeni-Boroujeni, Amir
• Iasonos, Alexia
• Selenica, Pier
• Brown, David N.
• Aghajanian, Carol
• Abu-Rustum, Nadeem R.
• Ellenson, Lora H.
• Weigelt, Britta

Titel

TERT promoter mutations and gene amplification in endometrial cancer

Ist Teil von

• Gynecologic oncology, 2023-12, Vol.179, p.16-23

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• To assess the clinicopathologic, molecular profiles, and survival outcomes of patients with endometrial carcinomas (ECs) harboring telomerase reverse transcriptase (TERT) hotspot mutations or gene amplification. ECs harboring somatic TERT promoter hotspot mutations or gene amplification (TERT-altered) were identified from 1944 ECs that underwent clinical tumor-normal sequencing from 08/2016–12/2021. Clinicopathologic variables, somatic mutation profiles, and survival outcomes of TERT-alt and TERT-wild-type EC were assessed. We identified 66 TERT-altered ECs (43 TERT-mutated and 23 TERT-amplified), representing 3% of the unselected ECs across histologic subtypes. Most TERT-altered ECs were of copy number (CN)-high/TP53abn molecular subtype (n = 40, 60%), followed by microsatellite-unstable (MSI-H) or CN-low/no specific molecular profile (NSMP)(n = 13, 20% each). TERT-amplified and TERT-mutated ECs were molecularly distinct, with TERT-amplified ECs being more genomically instable and more frequently harboring TP53 and PPP2R1A alterations (q < 0.1). Compared to TERT-wild-type ECs, TERT-altered ECs were more commonly of CN-H/TP53abn molecular subtype (31% vs 57%, p = 0.001), serous histology (10% vs 26%, p = 0.004), and were significantly enriched for TP53, CDKN2A/B, and DROSHA somatic genetic alterations (q < 0.1). Median progression-free survival was 18.7 months (95% CI 11.8–not estimable [NE]) for patients with TERT-altered EC and 80.9 months (65.8-NE) for patients with TERT-wild-type EC (HR 0.33, 95% CI 0.21–0.51, p < 0.001). Similarly, median overall survival was 46.7 months (95% CI 30-NE) for TERT-altered EC patients and not reached for TERT-wild-type EC patients (HR 0.24, 95% CI 0.13–0.44, p < 0.001). TERT-altered ECs, although rare, are enriched for CN-high/TP53abn tumors, TP53, CDKN2A/B and DROSHA somatic mutations, and independently predict worse survival outcomes. •TERT promoter hotspot mutations and gene amplification in endometrial cancer (EC) are rare.•TERT alterations are enriched in high-risk ECs.•Patients with TERT-altered EC have inferior survival outcomes compared to those with TERT-wild-type EC.•TERT alteration stratifies survival outcomes of CN-H/TP53abn molecular subtype ECs.•Within TERT-altered ECs, TERT-amplified ECs are enriched for TP53 and PPP2R1A mutations compared to TERT-mutated ECs.