Abstract C058: Clinical relevance of telomerase upregulation via TERT promoter mutation or TERC amplification in high-grade ovarian cancer

• Published in: Molecular cancer therapeutics 2023-12, Vol.22 (12_Supplement), p.C058-C058
• Main Authors: Blanc-Durand, Felix, Ngoi, Natalie, Vasseur, Damien, Pautier, Patricia, Michels, Judith, Ouali, Kaissa, Genestie, Catherine, Cotteret, Sophie, Rouleau, Etenne, Lim, Yi Wan, Lim, Siew Eng, Lim, Diana, Wijaya, Silvana Talisa, Leary, Alexandra, Tan, David SP
• Format: Article
• Language: English
• ISSN: 1538-8514; 1538-8514
• DOI: 10.1158/1535-7163.TARG-23-C058

Background: Increased telomerase activity confers a survival advantage to cancer cells and is considered one of the cancer hallmarks. The two main molecular mechanisms responsible for telomerase upregulation are the amplification of the telomerase RNA component gene (TERCamp) which serves as the template for telomeric repeats, and mutations in the telomerase reverse transcriptasegene promoter (TERTm), which encored the catalytic unit of telomerase. Increased telomerase activity has been detected in more than 90% of ovarian cancer (OC) but the clinical impact of this phenotype remains understudied. Methods: This retrospective analysis included all patients (pts) with high grade OC who underwent large-panel sequencing (Foundation Medicine) from National University Cancer Institute, Singapore and Institut Gustave Roussy, France. TERTm and TERCamp were correlated with clinical, pathological and molecular features as well as progression-free survival (PFS, calculated from histological diagnosis to first progression). Results: Out of the 503 pts with OC analyzed, 15 pts (3.0%) presented TERT mutation and 39 pts (7.8%) had TERC amplification. In the TERTm subgroup, only one hotspot mutation was detected (c.-124C>T). Compared to the wild-type (WT) group, there was significantly higher frequency of FIGO I/II diseases (57% vs 17%, p=0.001) and clear-cell histology (80% vs 14%, p