Clinical significance of genetic profiling based on different anatomic sites in patients with mucosal melanoma who received or did not receive immune checkpoint inhibitors

Cancer Cell International

Research

Kai-Hua Guo¹  Kuntai Jiang²  Xiao-Yan Wu²  Ling Deng²  Xin-Hua Yang²  Fang Wang²  Hai-Yun Wang³  Ye Liu⁴ 

[1] Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road, 510080, Guangzhou, P. R. China;Department of Molecular Diagnostics, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 510060, Guangzhou, P. R. China;Department of Pathology, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, National Children’s Medical Center for South Central Region, 510623, Guangzhou, P. R. China;Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, National Children’s Medical Center for South Central Region, 510623, Guangzhou, P. R. China;Shenzhen Hospital, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 518116, Shenzhen, China;Department of Molecular Diagnostics, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 510060, Guangzhou, P. R. China;

关键词: Mucosal melanoma;    Clinical significance;    Primary site;    Prognosis;    Genetic alterations;   

DOI  :  10.1186/s12935-023-03032-3

 received in 2023-04-23, accepted in 2023-08-15,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundTo date, data on the efficacy of targeted therapies for mucosal melanoma (MM) are limited. In this study, we analyzed genetic alterations according to the primary site of origin, which could provide clues for targeted therapy for MM.MethodsWe conducted a retrospective cohort study of 112 patients with MM. Targeted sequencing was performed to analyze genetic aberrations. Kaplan–Meier analysis was conducted with the log-rank test to compare the significance among subgroups.ResultsIn total, 112 patients with MM were included according to the anatomic sites: 38 (33.9%) in the head and neck, 22 (19.6%) in the genitourinary tract, 21 (18.8%) in the anorectum, 19 (17.0%) in the esophagus, 10 (8.9%) in the uvea, and 2 (1.8%) in the small bowel. The most significantly mutated genes included BRAF (17%), KIT (15%), RAS (15%), TP53 (13%), NF1 (12%), SF3B1 (11%), GNA11 (7%), GNAQ (5%), and FBXW7 (4%). A large number of chromosomal structural variants was found. The anatomic sites of esophagus and small bowel were independent risk factors for progression-free survival (PFS, hazard ratio [HR] 4.78, 95% confidence interval [CI] 2.42–9.45, P < 0.0001) and overall survival (OS, HR 5.26, 95% CI 2.51–11.03, P < 0.0001). Casitas B-lineage lymphoma (CBL) mutants showed significantly poorer PFS and OS. In contrast, MM patients who received immune checkpoint inhibitors (ICIs) had a significantly more favorable OS (HR 0.39, 95% CI 0.20–0.75, P = 0.008).ConclusionsOur findings reveal the genetic features of patients with MM, mainly across six anatomic sites, offering a potential avenue for targeted therapies.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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