Candidate therapeutic agents in a newly established triple wild-typemucosalmelanoma cell line

作     者：Chaoji Shi Ziyue Gu Shengming Xu Houyu Ju Yunteng Wu Yong Han Jiayi Li Chuwen Li Jing Wu Lizhen Wang Jiang Li Guoyu Zhou Weimin Ye Guoxin Ren Zhiyuan Zhang Rong Zhou 

作者机构：Department of Oral and Maxillofacial-Head Neck OncologyShanghai Ninth People’s HospitalCollege of StomatologyShanghai Jiao Tong University School of MedicineShanghai 200011P.R.China National Clinical Research Center for Oral DiseasesShanghai 200011P.R.China Shanghai Key Laboratory of Stomatology&Shanghai Research Institute of StomatologyShanghai 200011P.R.China Research Unit of Oral and Maxillofacial Regenerative MedicineChinese Academy of Medical SciencesShanghai 200011P.R.China Department of Oral PathologyNinth People’s HospitalShanghai Jiao Tong UniversitySchool of MedicineShanghai 200011P.R.China 

出 版 物：《Cancer Communications》 (癌症通讯（英文）)

年 卷 期：2022年第42卷第7期

页      面：627-647页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：National Natural Science Foundation of China,Grant/Award Number:82002862 China Association for Science and Technology,Grant/Award Number:2019QNRC001 Shanghai Clinical Research Center for Oral Diseases,Grant/Award Number:19MC1910600 CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2019-I2M-5-037 Shanghai Municipal Key Clinical Specialty,Grant/Award Number:shslczdzk01601 Emerging Frontier Technology Joint Research Project,Grant/Award Number:SHDC12018104 

主　　题：bortezomib cell line extrachromosomal DNA high-throughput drug screening mucosal melanoma patient derived tumor cells patient-derived xenograft whole-genome sequencing 

摘      要：Background:Mucosalmelanoma has characteristically distinct genetic features and typically poor *** lack of representativemucosal melanoma models,especially cell lines,has hindered translational research on this melanoma *** this study,we aimed to establish and provide the biological properties,genomic features and the pharmacological profiles of a mucosal melanoma cell line that would contribute to the understanding and treatment optimization of molecularly-defined mucosal melanoma ***:The sample was collected from a 67-year-old mucosal melanoma patient and processed into pieces for the establishment of cell line and patientderived xenograft(PDX)*** proliferation and tumorigenic property of cancer cells from different passageswere evaluated,andwhole-genome sequencing(WGS)was performed on the original tumor,PDX,established cell line,and the matched blood to confirm the establishment and define the genomic features of this cell *** was conducted to depict the architecture of amplified regions detected by ***-throughput drug screening(HTDS)assay including a total of 103 therapeutic agents was implemented on the established cell line,and selected candidate agents were validated in the corresponding PDX ***:A mucosal melanoma cell line,MM9H-1,was established which exhibited robust proliferation and tumorigenicity after more than 100 serial *** analysis of MM9H-1,corresponding PDX,and the original tumor showed genetic fidelity across genomes,and MM9H-1 was defined as a triple wild-type(TWT)melanoma subtype lacking well-characterized“driver mutations.Instead,the amplification of several oncogenes,telomerase reverse transcriptase(TERT),v-Rafmurine sarcoma viral oncogene homolog B1(BRAF),melanocyte Inducing transcription factor(MITF)and INO80 complex ATPase subunit(INO80),via large-scale genomic rearrangement potentially contributed to oncogenesis of ***,HTDS identified proteasome