Huan Li1, Lujing Yang1, Yumei Lai1, Xintong Wang2, Xinyin Han3,4, Siyao Liu2, Dongliang Wang2, Xiaojuan Li2, Nana Hu2, Yan Kong5, Lu Si6, Zhongwu Li7. 1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Fucheng Road No.52, Haidian District, Peking, 100142, Beijing, People's Republic of China. 2. ChosenMed Technology (Beijing) Co., Ltd., Beijing, 100176, People's Republic of China. 3. Computer Network Information Center, Chinese Academy of Sciences, Beijing, 100190, People's Republic of China. 4. University of the Chinese Academy of Sciences, Beijing, 100190, People's Republic of China. 5. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Fucheng Road No.52, Haidian District, 100142, Beijing, People's Republic of China. k-yan08@163.com. 6. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Fucheng Road No.52, Haidian District, 100142, Beijing, People's Republic of China. silu15_silu@126.com. 7. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Fucheng Road No.52, Haidian District, Peking, 100142, Beijing, People's Republic of China. zhwuli@hotmail.com.
Abstract
BACKGROUND: Rectal mucosal melanoma (RMM) is a rare and highly aggressive disease with a poor prognosis. Due to the rarity of RMM, there are few studies focusing on its genetic mechanism. This retrospective study aimed to analyze the genetic spectrum and prognosis of RMM in China and lay a foundation for targeted therapy. METHODS: 36 patients with primary RMM from Peking University Cancer Hospital were enrolled in this study. The Next-generation sequencing (NGS) data of the tumor samples were fitted into the TruSight™ Oncology 500 (TSO500) Docker pipeline to detect genomic variants. Then, the univariate and multivariate Cox hazard analysis were performed to evaluate the correlations of the variants with the overall survival (OS), along with Kaplan-Meier and log-rank test to determine their significance. RESULTS: BRAF mutations, NRG1 deletions and mitotic index were significant prognostic factors in the univariate analysis. In multivariable analysis of the OS-related prognostic factors in primary RMM patients, it revealed 2 significant alterations: BRAF mutations [HR 7.732 (95%CI: 1.735-34.456), P = 0.007] and NRG1 deletions [HR 14.976 (95%CI: 2.305-97.300), P = 0.005]. CONCLUSIONS: This is the first study to show genetic alterations exclusively to Chinese patients with RMM. We confirmed genetic alterations of RMM differ from cutaneous melanoma (CM). Our study indicates that BRAF and NRG1 were correlated with a poor prognostic of RMM and may be potential therapeutic targets for RMM treatment.
BACKGROUND:Rectal mucosal melanoma (RMM) is a rare and highly aggressive disease with a poor prognosis. Due to the rarity of RMM, there are few studies focusing on its genetic mechanism. This retrospective study aimed to analyze the genetic spectrum and prognosis of RMM in China and lay a foundation for targeted therapy. METHODS: 36 patients with primary RMM from Peking University Cancer Hospital were enrolled in this study. The Next-generation sequencing (NGS) data of the tumor samples were fitted into the TruSight™ Oncology 500 (TSO500) Docker pipeline to detect genomic variants. Then, the univariate and multivariate Cox hazard analysis were performed to evaluate the correlations of the variants with the overall survival (OS), along with Kaplan-Meier and log-rank test to determine their significance. RESULTS:BRAF mutations, NRG1 deletions and mitotic index were significant prognostic factors in the univariate analysis. In multivariable analysis of the OS-related prognostic factors in primary RMMpatients, it revealed 2 significant alterations: BRAF mutations [HR 7.732 (95%CI: 1.735-34.456), P = 0.007] and NRG1 deletions [HR 14.976 (95%CI: 2.305-97.300), P = 0.005]. CONCLUSIONS: This is the first study to show genetic alterations exclusively to Chinese patients with RMM. We confirmed genetic alterations of RMM differ from cutaneous melanoma (CM). Our study indicates that BRAF and NRG1 were correlated with a poor prognostic of RMM and may be potential therapeutic targets for RMM treatment.
Authors: Adrienne Callahan; William F Anderson; Sital Patel; Jill S Barnholtz-Sloan; Jeremy S Bordeaux; Margaret A Tucker; Meg R Gerstenblith Journal: Dermatol Surg Date: 2016-01 Impact factor: 3.398
Authors: Danielle M Bello; Elizabeth Smyth; Daniel Perez; Shaheer Khan; Larissa K Temple; Charlotte E Ariyan; Martin R Weiser; Richard D Carvajal Journal: Dis Colon Rectum Date: 2013-02 Impact factor: 4.585