e13655 Background: The reactivation of telomerase reverse transcriptase ( TERT) is one of the characters that make cancer cells immortal. TERT expression has been shown in various human cancers.However, the landscape of TERT alterations in Chinese patients with solid tumors still remains unclear. Here, we illustrated the profile of TERT variations of Chinese solid tumor patients by using next generation sequencing (NGS)-based targeted sequencing. Methods: Formalin fixed, paraffin embedded (FFPE) tumor tissues and matching blood samples were collected from 9874 Chinese patients and subjected to a NGS-based panel at a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. All classes of alterations were assessed. Results: FFPE samples from 9874 Chinese solid tumor patients included lung cancers (39.7%), liver cancers (12.5%), colorectal cancers (10.8%), gastric cancers (5.7%), pancreatic cancers (4.9%), biliary tract tumors (4.6%), and other 18 cancer types (21.7%) were assessed. And 1187 (12.0%) out of 9874 cancer samples had TERT variations. TERT variations occurred in all types of cancer with various frequencies: urothelial neoplasms (52.0%), central nervous system tumors (40.0%), melanomas (38.9%), liver cancers (30.7%), thyroid tumors (24.3%), cervical cancers (20.6%), biliary tract tumors (16.3%), head and neck tumors (14.6%), soft tissue tumors (12.2%) and lung cancers (10.3%). Substitution was the most common variation of TERT and accounted for 58.7% of all the alterations, followed by gene amplification (38.8%) and fusions (2.4%). There were 86.8% of substitution variations presented in TERT promoter region comprising of c.-124C > T (70.7%) and c.-146C > T (13.1%). Patients with TERT alterations included 414 females and 773 males with a median age of 59 years old (range: 8-88). Tumors included stage IV (34.0%), stage III (22.2%), stage II (12.7%), stage I (18.7%) and stage 0 (12.3%). TERT variations were correlated with patients’ age (p = 0.00083) and gender (p = 5.59×10−7). There was no significant correlation of TERT alterations with the highly mutated TP53. The frequencies of TERT alterations were similar in patients with mutated and wild type TP53 (12.7% vs 11.1%). Conclusions: Our study revealed that 12.0% Chinese solid tumor patients harbored TERT alterations, especially two hotspots mutations (c.-124C > T and c.-146C > T) in the promoter region. TERT variations had a correlation with patients’ age and gender, but no correlation with hotspot TP53 mutations.
Radiation therapy for biliary tract tumors: the joint experience of three centers*