Presence of TERT Promoter Mutations is a Secondary Event and Associates with Elongated Telomere Length in Myxoid Liposarcomas

International Journal of Molecular Sciences

TimH. Brümmendorf¹  Barbara Voss¹  Fabian Beier¹  Martina Crysandt¹  Edgar Jost¹  MonicaS. Ventura Ferreira¹  Anne-Sophie Bouillon¹  Ruth Knuechel²  Till Braunschweig² 

[1] Department of Hematology, Oncology, Haemostaseology and Stem Cell Transplantation, RWTH Aachen University Medical Faculty, 52074 Aachen, Germany;Institute of Pathology, RWTH Aachen University Medical Faculty, 52074 Aachen, Germany;

关键词: myxoid liposarcoma;    sarcoma;    telomere;    telomerase;    TERT promoter mutation;   

DOI  :  10.3390/ijms19020608

来源: DOAJ

【 摘 要 】

The occurrence of TERT promoter mutations has been well described in soft tissue sarcomas (STS). However, the biological role of these mutations as well as their impact on telomere length in STS is still unclear. We analyzed 116 patient samples diagnosed with 22 distinct histological subtypes of bone and STS for the occurrence of TERT promoter mutations by Sanger sequencing. We observed TERT promoter mutations at an overall frequency of 9.5% distributed over 7 different sarcoma subtypes. Except for one chondrosarcoma case harboring a C250T mutation, all other mutations were detected at location C228T. By far the far highest frequency of TERT promoter mutations was found in myxoid liposarcoma (MLS) (4 out of 9 cases studied, i.e., 44%). Assessment of telomere length from tumor biopsies revealed that TERT promoter-mutated MLSs had significantly fewer shortened telomeres in comparison to TERT wildtype MLSs. Based on the frequency of TERT promoter mutations and the elongated telomere length in mutated compared to wildtype MLS, we hypothesize that occurrence of TERT promoter mutations has a pivotal role in the disease progression as a secondary genetic event at a time when tumor cells face the need for telomere elongation to allow further proliferation.

【 授权许可】

Unknown