Uncommon Human Telomerase Reverse Transcriptase Promoter Mutations Are Associated With Poor Survival in Ovarian Clear Cell Carcinoma

• Published in: American journal of clinical pathology Vol. 149; no. 4; pp. 352 - 361
• Main Authors: Nishikimi, Kyoko, Nakagawa, Kiyoshi, Tate, Shinichi, Matsuoka, Ayumu, Iwamoto, Masami, Kiyokawa, Takako, Shozu, Makio
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 07.03.2018
• Subjects: Adenocarcinoma, Clear Cell - genetics; Adenocarcinoma, Clear Cell - mortality; Adenocarcinoma, Clear Cell - pathology; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Carcinoma, Ovarian Epithelial; Cell survival; Deoxyribonucleic acid; DNA; Female; Humans; Medical prognosis; Middle Aged; Mutation; Mutation hot spots; Neoplasms, Glandular and Epithelial - genetics; Neoplasms, Glandular and Epithelial - mortality; Neoplasms, Glandular and Epithelial - pathology; Nucleotide sequence; Ovarian Neoplasms - genetics; Ovarian Neoplasms - mortality; Ovarian Neoplasms - pathology; Paraffin; Prognosis; Promoter Regions, Genetic; Retrospective Studies; RNA-directed DNA polymerase; Survival Analysis; Telomerase; Telomerase - genetics; Telomerase reverse transcriptase; Ovarian clear cell carcinoma; promoter mutation; Adenofibroma
• ISSN: 0002-9173; 1943-7722
• DOI: 10.1093/ajcp/aqx166

Abstract Objectives The present study assessed whether human telomerase reverse transcriptase (TERT) promoter mutations mediate the increased mortality risk observed in patients with ovarian clear cell carcinoma (CCC) and characterized the pathologic features of TERT promoter mutation-associated ovarian CCC. Methods The TERT promoter region in genomic DNA extracted from paraffin-embedded ovarian CCC specimens (n = 93) was bidirectionally sequenced. Results A total of 24 TERT promoter mutations were identified among the analyzed CCC cases, of which 11 were known “hotspot” mutations whose frequency was increased in CCC cases with compared to without coexistent adenofibroma (P < .05). In contrast, the 14 (including three novel) identified uncommon site mutations were shown to be associated with a poor progression-free survival rate (P < .01). Conclusions The identified uncommon TERT promoter mutations exacerbate the poor prognosis characteristic of ovarian CCC cases, and the hotspot mutations appear to be a molecular feature of the adenofibroma-associated form of the disease.