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

Hai-Yun Wang; Ye Liu; Ling Deng; Kuntai Jiang; Xin-Hua Yang; Xiao-Yan Wu; Kai-Hua Guo; Fang Wang

doi:10.1186/s12935-023-03032-3

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 Int. 2023 Aug 30;23(1):187. doi: 10.1186/s12935-023-03032-3.

Authors

Hai-Yun Wang^{1

2}, Ye Liu^{3

4}, Ling Deng⁴, Kuntai Jiang⁴, Xin-Hua Yang⁴, Xiao-Yan Wu⁴, Kai-Hua Guo⁵, Fang Wang⁶

Affiliations

¹ 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.
² 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.
³ 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.
⁴ 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.
⁵ Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road, 510080, Guangzhou, P. R. China. guokh@mail.sysu.edu.cn.
⁶ 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. wangfang@sysucc.org.cn.

Abstract

Background: To 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.

Methods: We 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.

Results: In 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).

Conclusions: Our findings reveal the genetic features of patients with MM, mainly across six anatomic sites, offering a potential avenue for targeted therapies.

Keywords: Clinical significance; Genetic alterations; Mucosal melanoma; Primary site; Prognosis.

Grants and funding

2020A1515010313/Natural Science Foundation of Guangdong Province