Comprehensive molecular findings in primary malignant melanoma of the esophagus: A multicenter study

Abstract

AbstractPrimary malignant melanoma of the esophagus (PMME) is an extremely rare but highly aggressive malignancy with a poor prognosis. Due to the scarcity of driver gene alterations, there is a need for more clinical data to comprehensively depict its molecular alterations. This study reviewed 26 PMME cases from three medical centers. Hybrid capture‐based targeted sequencing of 295 and 1021 genes was performed in 14 and 12 cases, respectively. We found that PMME patients had a relatively low tumor mutation burden (median, 2.88 mutations per Mb) and were simultaneously accompanied by mutations in genes such as KIT (6/26, 23%), TP53 (6/26, 23%), SF3B1 (4/26, 15%), and NRAS (3/26, 12%). KIT, NRAS, and BRAF were mutually exclusive, and SF3B1 co‐occurred with KIT mutation and amplification. The most common pathways affected were the mitogen‐activated protein kinases and DNA damage response (DDR) pathways. Stage IV was a risk factor for both progression‐free survival (hazard ratio [HR] = 5.14, 95% confidence interval [CI] = 1.32–19.91) and overall survival (OS), HR = 4.33, 95% CI = 1.22–15.30). Treatment with immune‐checkpoint inhibitors (ICIs) was an independent factor for favorable OS (HR = 0.10, 95% CI = 0.01–0.91). Overall, PMME is a complex malignancy with diverse gene alterations, especially with harboring DDR alterations for potentially response from ICIs.