Telomere Maintenance Associated Mutations in the Genetic Landscape of Gynecological Mucosal Melanoma
FRONTIERS IN ONCOLOGY
Authors: Yuan, Guangwen; Song, Jinge; Li, Ning; Song, Qianqian; Li, Yifei; Du, Yingxi; Wang, Xiaobing; Jiao, Yuchen; Wu, Lingying
Abstract
Purpose Gynecological melanomas (GMs) are rare tumors with a poor prognosis. Here, we performed exome sequencing to generate the mutational landscape of GMs. Methods Next-generation sequencing was carried out on mucosal melanoma samples (n= 35) obtained from gynecological sites. The alternative telomere lengthening (ALT) phenotype was verified by fluorescencein situhybridization and the C-circle assay. Immunohistochemistry was performed to detect ATRX protein. Copy number variations inTERTwere detected by droplet digital polymerase chain reaction. Results In the 58 formalin-fixed paraffin-embedded samples, we identified 33 (56.9%) ALT-positive cases, with 23 showing loss of ATRX protein.TERTpromoter mutation was not detected in GMs (n= 40), but copy number variations in theTERTregion were observed in 20% (7/35) of the samples.TERTamplification was mutually exclusive with ALT (P< 0.05). Kaplan-Meier revealed that ALT relative toTERTamplification was associated with longer overall survival in GM patients without metastasis. Conclusion These findings indicate that telomere maintenance mechanisms play a critical role in the tumorigenesis of GMs and may aid in the prediction of clinical prognosis and the development of targeted therapy for the treatment of GM.
Genetic profile of non-small cell lung cancer (NSCLC): A hospital-based survey in Jinhua
MOLECULAR GENETICS & GENOMIC MEDICINE
Authors: Chen, Xianguo; Xu, Bo; Li, Qiang; Xu, Xiaoyi; Li, Xianshuai; You, Xia; Yu, Zhaonan
Abstract
Background: We describe the clinical features, genetic profile, and their correlation in NSCLC patients. Methods: A total of 256 Chinese patients with NSCLC were enrolled in this study. NGS-based genomic profiling of major lung cancer-related genes was performed on formalin-fixed paraffin-embedded tumor samples. Results: Of 256 patients with NSCLC, 219 were adenocarcinoma and most of them were in the early stage. Among patients, 63.3% patients have more than two gene mutations. By analyzing variant allele frequency (VAF), we found that the median VAF has significant differences between squamous cell carcinoma and adenocarcinoma, as well as early stage and advanced stage. The frequency of mutations in EGFR, MET, and RET were significantly higher in nonsmokers than in smokers. Besides, Pearson correlation analysis found that ALK, BRAF, and MET mutations had a strong correlation with age. Notably, higher frequencies of ALK and BRAF alterations were associated with younger age, while more frequent MET mutations appear in the patients at age 55 or older. Conclusion: More unique features of cancer driver genes in Chinese NSCLC were identified by next-generation sequencing. These findings highlighted that it is necessary to carry out targeted detection according to different clinical features for NSCLC.