Genomic and Transcriptional Profiling of Chinese Melanoma Patients Enhanced Potentially Druggable Targets: A Multicenter Study

Background: In contrast to Caucasian melanoma, which has been extensively studied, there are few studies on melanoma in Asian populations. Sporadic studies reported that only 40% of Asian melanoma patients could be druggable, which was much lower than that in Caucasians. More studies are required to...

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Main Authors: Yue Li, Baoming Wang, Chunyang Wang, Dandan Zhao, Zhengchuang Liu, Yanling Niu, Xiaojuan Wang, Wei Li, Jianhua Zhu, Houquan Tao, Tonghui Ma, Tao Li
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/15/1/283
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author Yue Li
Baoming Wang
Chunyang Wang
Dandan Zhao
Zhengchuang Liu
Yanling Niu
Xiaojuan Wang
Wei Li
Jianhua Zhu
Houquan Tao
Tonghui Ma
Tao Li
author_facet Yue Li
Baoming Wang
Chunyang Wang
Dandan Zhao
Zhengchuang Liu
Yanling Niu
Xiaojuan Wang
Wei Li
Jianhua Zhu
Houquan Tao
Tonghui Ma
Tao Li
author_sort Yue Li
collection DOAJ
description Background: In contrast to Caucasian melanoma, which has been extensively studied, there are few studies on melanoma in Asian populations. Sporadic studies reported that only 40% of Asian melanoma patients could be druggable, which was much lower than that in Caucasians. More studies are required to refine this conclusion. Methods: Chinese melanoma patients (<i>n</i> = 469) were sequentially sequenced by DNA-NGS and RNA-NGS. The genomic alterations were determined, and potentially actionable targets were investigated. Results: Patients with potential druggable targets were identified in 75% of Chinese melanoma patients by DNA-NGS based on OncoKB, which was much higher than in a previous Asian study. <i>NRG1</i> fusions were first identified in melanoma. In addition, up to 11.7% (7/60) of patients in the undruggable group could be recognized as actionable by including RNA-NGS analysis. By comparing the fusion detection rate between DNA-NGS and RNA-NGS, all available samples after DNA-NGS detection were further verified by RNA-NGS. The use of RNA-NGS enhanced the proportion of druggable fusions from 2.56% to 17.27%. In total, the use of RNA-NGS increased the druggable proportion from 75% to 78%. Conclusions: In this study, we systemically analyzed the actionable landscape of melanoma in the largest Asian cohort. In addition, we first demonstrated how DNA and RNA sequential sequencing is essential in bringing clinical benefits to more patients with melanoma.
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spelling doaj.art-b5414887542f41fea66696808338a65e2023-11-16T15:04:08ZengMDPI AGCancers2072-66942022-12-0115128310.3390/cancers15010283Genomic and Transcriptional Profiling of Chinese Melanoma Patients Enhanced Potentially Druggable Targets: A Multicenter StudyYue Li0Baoming Wang1Chunyang Wang2Dandan Zhao3Zhengchuang Liu4Yanling Niu5Xiaojuan Wang6Wei Li7Jianhua Zhu8Houquan Tao9Tonghui Ma10Tao Li11Harbin Medical University Cancer Hospital, Harbin 150040, ChinaJichenjunchuang Clinical Laboratory, Hangzhou 310022, ChinaJichenjunchuang Clinical Laboratory, Hangzhou 310022, ChinaJichenjunchuang Clinical Laboratory, Hangzhou 310022, ChinaKey Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, ChinaJichenjunchuang Clinical Laboratory, Hangzhou 310022, ChinaJichenjunchuang Clinical Laboratory, Hangzhou 310022, ChinaJichenjunchuang Clinical Laboratory, Hangzhou 310022, ChinaJichenjunchuang Clinical Laboratory, Hangzhou 310022, ChinaKey Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, ChinaJichenjunchuang Clinical Laboratory, Hangzhou 310022, ChinaInstitute of Basic Medicine and Cancer (IBMC), Department of Bone and Soft-tissue Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou 310022, ChinaBackground: In contrast to Caucasian melanoma, which has been extensively studied, there are few studies on melanoma in Asian populations. Sporadic studies reported that only 40% of Asian melanoma patients could be druggable, which was much lower than that in Caucasians. More studies are required to refine this conclusion. Methods: Chinese melanoma patients (<i>n</i> = 469) were sequentially sequenced by DNA-NGS and RNA-NGS. The genomic alterations were determined, and potentially actionable targets were investigated. Results: Patients with potential druggable targets were identified in 75% of Chinese melanoma patients by DNA-NGS based on OncoKB, which was much higher than in a previous Asian study. <i>NRG1</i> fusions were first identified in melanoma. In addition, up to 11.7% (7/60) of patients in the undruggable group could be recognized as actionable by including RNA-NGS analysis. By comparing the fusion detection rate between DNA-NGS and RNA-NGS, all available samples after DNA-NGS detection were further verified by RNA-NGS. The use of RNA-NGS enhanced the proportion of druggable fusions from 2.56% to 17.27%. In total, the use of RNA-NGS increased the druggable proportion from 75% to 78%. Conclusions: In this study, we systemically analyzed the actionable landscape of melanoma in the largest Asian cohort. In addition, we first demonstrated how DNA and RNA sequential sequencing is essential in bringing clinical benefits to more patients with melanoma.https://www.mdpi.com/2072-6694/15/1/283melanomaDNA-NGSRNA-NGSsequencetarget
spellingShingle Yue Li
Baoming Wang
Chunyang Wang
Dandan Zhao
Zhengchuang Liu
Yanling Niu
Xiaojuan Wang
Wei Li
Jianhua Zhu
Houquan Tao
Tonghui Ma
Tao Li
Genomic and Transcriptional Profiling of Chinese Melanoma Patients Enhanced Potentially Druggable Targets: A Multicenter Study
Cancers
melanoma
DNA-NGS
RNA-NGS
sequence
target
title Genomic and Transcriptional Profiling of Chinese Melanoma Patients Enhanced Potentially Druggable Targets: A Multicenter Study
title_full Genomic and Transcriptional Profiling of Chinese Melanoma Patients Enhanced Potentially Druggable Targets: A Multicenter Study
title_fullStr Genomic and Transcriptional Profiling of Chinese Melanoma Patients Enhanced Potentially Druggable Targets: A Multicenter Study
title_full_unstemmed Genomic and Transcriptional Profiling of Chinese Melanoma Patients Enhanced Potentially Druggable Targets: A Multicenter Study
title_short Genomic and Transcriptional Profiling of Chinese Melanoma Patients Enhanced Potentially Druggable Targets: A Multicenter Study
title_sort genomic and transcriptional profiling of chinese melanoma patients enhanced potentially druggable targets a multicenter study
topic melanoma
DNA-NGS
RNA-NGS
sequence
target
url https://www.mdpi.com/2072-6694/15/1/283
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