Genetic Alteration of Chinese Patient With Rectal Mucosal Melanoma

Abstract

BACKGROUNDRectal mucosal melanoma (RMM) is an aggressive disease with a poor prognosis. Due to the rarity of RMM, few studies about genetic mechanism of the malignant tumor have been conducted. This retrospective study aimed to analyze the mutation spectrum of RMM in China and lay a foundation for targeted therapy.METHODSNext-generation sequencing was performed in 36 patients with primary RMM in Peking University Cancer Hospital from May 2010 to March 2019. TMB estimates were determined applying the TruSight Oncology 500 targeted sequencing panel. Survival analysis was performed with Kaplan-Meier, log-rank test.RESULTSNRG1 deletions, BRAF mutations and mitotic index were significant prognostic factors in the univariate analysis. In multivariable analysis in overall survival of the prognostic factors in primary RMM patients, it revealed 2 significant variables: NRG1 deletions [HR = 8.830 (95%CI: 1.026–76.026), P = 0.047)]and BRAF mutations [HR = 7.877 (95%CI: 1.158–53.603), P = 0.035].CONCLUSIONSThis is the first study to show genetic alterations exclusively to Chinese patients with RMM. Although the sample size of the current study is relatively small, we confirmed genetic mutations of RMM differs from cutaneous melanoma. Our study indicates that BRAF and NRG1 may be potential therapeutic targets for rectal mucosal melanoma treatment. AKT3/KCNH1 fusion was correlated with a poor prognostic of RMM.