Analysis of Chinese acral and mucosal melanoma patient genomic and neoantigen profiles in cancer vaccine development: A pilot study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14300-e14300 ◽  
Author(s):  
Xianling Guo ◽  
Song Gao ◽  
Li Yang ◽  
Juemin Fang ◽  
Guochao Wei ◽  
...  
Keyword(s):  
Pilot Study ◽  
Cutaneous Melanoma ◽  
Vaccine Development ◽  
Mucosal Melanoma ◽  
The Cancer Genome Atlas ◽  
Driver Mutations ◽  
Data Set ◽  
Acral Melanoma ◽  
Tumor Mutational Burden ◽  
Melanoma Patients

e14300 Background: Acral and mucosal melanoma are rare subtypes accounting for about 3% of all melanoma cases. The cutaneous melanoma genomic landscape is well defined; however, little is known about the acral and mucosal melanoma mutational spectrum. In this pilot study, we evaluated the genomic and neo-antigen profiles and tumor mutational burden (TMB) from acral and mucosal melanoma patients with the aim of designing personalized vaccines and longitudinally tracking patients’ clinical courses. Methods: Tumor whole exome sequencing and neo-antigen profiling of 5 acral and 3 mucosal melanoma patients at Shanghai Tenth Peoples Hospital, Tongji University, China between April 2018 and January 2019 was performed using YuceBio’s proprietary analytics platform. Watsonä for Genomics, an artificial intelligence decision-support system, was used for variant interpretation and annotation. A comparative analysis was performed on Chinese acral melanoma data with the published Caucasian acral cohort from the Translational Genomics Research Institute (TGen) and The Cancer Genome Atlas (TCGA) predominantly Caucasian cutaneous melanoma data set. Results: TMB in our acral/mucosal melanoma cohort was 2.26/Megabase (Mb) compared to over 20/Mb in published cutaneous melanoma studies. Tumor neo-antigen burden (TNAB) in our group was 1.03 neo-epitopes/Mb. Low TNAB levels were associated with low TMB levels in all tumors. Incidence of BRAF and NRAS mutant cases in our cohort was 0% (0/8) and 13% (1/8) respectively compared to 19% (5/27) and 7% (2/27) of the Caucasian acral population in the TGen dataset. Incidence of BRAF and NRAS mutations in the TCGA cutaneous melanoma dataset was 54% (237/440) and 28% (125/440), respectively. Conclusions: TMB was significantly lower in acral/mucosal than in cutaneous melanoma and may be a surrogate for TNAB. Detection of BRAF and NRAS mutations, the two most prevalent driver mutations in cutaneous melanoma, were significantly lower frequencies in both Chinese and Caucasian acral melanoma patients in this study, suggesting alternate cancer drivers may exist in this subtype. Strategies to address challenges of low TNAB in vaccine development are being explored.

Cutaneous melanoma mutation pathways and driver mutations as racially biased.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22066-e22066
Author(s):  
Margaret I Sanchez ◽  
James Michael Grichnik
Keyword(s):  
Oxidative Damage ◽  
Racial Differences ◽  
Cutaneous Melanoma ◽  
The Cancer Genome Atlas ◽  
Driver Mutations ◽  
Racial Groups ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
Cancer Genome Atlas ◽  
Substitution Mutations

e22066 Background: Cutaneous melanoma (CM) demonstrates differences in its clinical prevalence in different racial groups. CM generally exhibits a high tumor mutational burden (TMB) and mutually exclusive driving mutations in NRAS, BRAF or KIT. TMB may be driven by different pathways including ultraviolet radiation (UVR), oxidation and deamination. UVR is the most common mutational signature found in CMs, but deamination and oxidation are also present. Methods: We analyzed 321 CMs exome data from The Cancer Genome Atlas network. BRAF, NRAS, KIT and those without (WT) were used to divide the melanomas. Germline SNPs with racial information (Caucasian, African and Asian) that were enriched in melanomas with a particular driving mutation were identified. Results: We compared the 3 racial groups across the 4 driving mutation types, Asian SNPs were significantly higher in KIT, African in WT and Caucasian in BRAF and NRAS. The melanomas were also evaluated by the type of substitution mutations including CC > TT for UV, G > T for oxidative damage and (G/A)C (G) > (G/A)T(G) for deamination. UV and deamination appeared inversely proportional, while oxidative damage appeared to be independent. UV signal was more prominent in BRAF and NRAS groups. KIT had a greater percentage of deamination while WT revealed more oxidative damage. We further compared UV and non-UV (CC > TT absence) KIT subgroups for racial differences. Asian SNPs were greatly increased in non-UV subgroup whereas Caucasian SNPs were in UV subgroup. Further, the non-UV KIT subgroup was divided into deamination and oxidative damage subgroups to compare racial differences. Deamination was significantly increased in Asians whereas oxidative damage was higher in Caucasians. In the case of the WT group, African SNPs were significantly higher in the non UV subgroup and were primarily correlated with oxidative damage. Conclusions: This study suggests that racial genetic background may predispose the distinctive mutational and genetic environments of melanoma development.

Adjuvant PD-1 inhibitor versus high-dose interferon α-2b for Chinese patients with cutaneous and acral melanoma: A retrospective cohort analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21516-e21516
Author(s):  
Jiuhong Wang ◽  
Jingjing Li ◽  
Xing Liu ◽  
Xizhi Wen ◽  
Dandan Li ◽  
...  
Keyword(s):  
Cutaneous Melanoma ◽  
Chinese Patients ◽  
Interferon Α ◽  
High Dose ◽  
Free Survival ◽  
Acral Melanoma ◽  
Treatment Groups ◽  
Melanoma Patients ◽  
Metastatic Sites ◽  
High Dose Interferon

e21516 Background: The clinical efficacy of PD-1 inhibitors as an adjuvant treatment for Asian melanoma patients has not yet been determined. Methods: Thus, this single-centre, retrospective study analysed the clinical data of 90 Chinese patients with completely resected, stage III cutaneous or acral melanoma who received either adjuvant PD-1 inhibitor or high-dose interferon α-2b (HDI). Propensity score matching (PSM) was used to control baseline differences between the two treatment groups. The primary end point was recurrence-free survival (RFS), and the secondary end points included distance metastasis-free survival (DMFS) and incidence of first distant metastatic sites. Results: Anti-PD-1 treatment resulted in significantly longer RFS (18-month RFS, 53.3% versus 26.7%; 95% CI, 0.097-0.975; P < 0.05) and DMFS (18-month DMFS, 70.9% versus 46.1%; 95% CI, 0.13-0.945; P < 0.05) than HDI in cutaneous melanoma patients. However, adjuvant anti-PD-1 treatment had no advantage over HDI in acral melanoma patients (18-month RFS, 30.0% versus 35.9%; P > 0.05; 18-month DMFS, 36.5% versus 63.6%; P > 0.05). The incidence of lung metastasis at first in the anti-PD-1 group was found to be significantly lower (12.5% versus 48.5%; P < 0.05) in cutaneous melanoma patients than in acral melanoma patients, but no difference in metastatic sites were observed between the two treatment groups among acral melanoma patients. The incidence of treatment-related AEs was similar between the two treatment groups. Conclusions: In conclusion, adjuvant anti-PD-1 treatment was well tolerated and yielded a significantly better prognosis than HDI in Chinese patients with stage IIIB/C cutaneous melanoma, but a significant difference was not observed in those with acral melanoma.

scholarly journals Genomic and Transcriptomic Characteristics According to Size of Papillary Thyroid Microcarcinoma

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1345
Author(s):  
Young Shin Song ◽  
Byung-Hee Kang ◽  
Seungbok Lee ◽  
Seong-Keun Yoo ◽  
Young Sik Choi ◽  
...  
Keyword(s):  
Early Stage ◽  
The Cancer Genome Atlas ◽  
Braf V600e ◽  
Papillary Thyroid Microcarcinoma ◽  
Driver Mutations ◽  
Papillary Thyroid ◽  
Targeted Next Generation Sequencing ◽  
Thyroid Microcarcinoma ◽  
Tert Promoter ◽  
Tumor Mutational Burden

It is controversial as to whether papillary thyroid microcarcinoma (PTMC) has some genomic and transcriptomic characteristics that differentiate between an early-stage lesion that would eventually evolve into the larger papillary thyroid cancer (PTC), and an occult indolent cancer in itself. To investigate this, we comprehensively elucidated the genomic and transcriptomic landscapes of PTMCs of different sizes, using a large-scaled database. This study included 3435 PTCs, 1985 of which were PTMCs. We performed targeted next-generation sequencing for 221 PTCs and integrated these data with the data including The Cancer Genome Atlas (TCGA) project. The frequency of v-raf murine sarcoma viral oncogene homolog B (BRAF)V600E mutation was higher in PTMCs >0.5 cm than that in very small PTMCs (≤0.5 cm) and decreased again in PTCs >2 cm. Among PTMCs, the prevalence of mutations in rat sarcoma (RAS) and telomerase reverse transcriptase (TERT) promoter was not significantly different according to their size, but lower than in large PTCs. There was no change in the tumor mutational burden, the number of driver mutations, and transcriptomic profiles with tumor size, among PTMCs and all PTCs. Although a few genes with differential expression and TERT promoter mutations were found in a few PTMCs, our findings showed that there were no useful genomic or transcriptomic characteristics for the prediction of the future progression of PTMC.

Characterization of the genetics of mucosal melanoma in patients treated with immunotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9556-9556
Author(s):  
Elizabeth Iannotti Buchbinder ◽  
Jason L. Weirather ◽  
Michael P. Manos ◽  
Ryan C. Brennick ◽  
Patrick Alexander Ott ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
High Response Rate ◽  
Mucosal Melanoma ◽  
Rare Type ◽  
Kit Mutation ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
Melanoma Patients ◽  
Mechanistic Basis

9556 Background: Mucosal melanomas can be effectively treated with checkpoint inhibitors, although the response rates are lower than those observed for melanomas arising in cutaneous sites. The mechanistic basis for the lower efficacy of immunotherapies in mucosal melanoma has been suggested to be related to their lower mutational burden. However, there has been limited characterization of the genetics in this melanoma subtype. Methods: Tumor genotyping was performed on all mucosal melanoma patients seen within the Dana Farber Cancer Institute from 2011 until the present by Oncopanel analysis. Results: We identified a total of 57 mucosal melanoma patients whose tumors had been genotyped. Of these 42 received immunotherapy and had response data available. Within the cohort of mucosal melanoma patients, 37.3% had durable clinical benefit (DCB) to their first line of IO therapy. These patients had an average mutational burden/megabase of 6.41 (95% CI 3.53-11.01) but tumor mutational burden did not correlate with response in this cohort. The pattern of mutations in mucosal melanomas was distinct from cutaneous melanomas, as the most frequent mutations were in SF3B1, ATRX, KIT and NF1 genes. Patients with KIT aberrations had a higher DCB rate compared patients with wildtype KIT (73 vs. 33%). In addition, there were several genetic differences observed based upon the site of origin of the mucosal melanoma. A higher rate of SF3B1 mutations was observed in patients with melanoma of anal/rectal origin while patients with vulvar/vaginal melanoma had higher rates of ATRX mutations, which frequently correlated with p53 ( TP53) mutations. Conclusions: This analysis is one of the first to look at genetic patterns in a large cohort of a relatively rare type of melanoma and correlate with response. Our findings confirm the low mutational burden observed in mucosal melanoma despite the high response rate observed in these patients. In addition, this study uncovered a higher rate of response to immunotherapy in mucosal melanoma patients with a KIT mutation.

scholarly journals Analysis of HSD11B2 as a prognostic marker in Melanoma via TCGA data mining

2020 ◽  
Author(s):  
Hongyi Fu ◽  
Yaqin Tang ◽  
Ying Ding
Keyword(s):  
Cox Regression ◽  
Signalling Pathway ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Rank Test ◽  
Clinicopathologic Characteristics ◽  
Data Set ◽  
Receptor Signalling ◽  
Pathologic Features ◽  
Melanoma Patients

Abstract Background: Hydroxysteroid 11-Beta Dehydrogenase 2 (HSD11B2) expression has been reported to be present in melanoma. We investigated the association of HSD11B2 with melanoma using publicly available data from The Cancer Genome Atlas (TCGA). Methods: The relationship between clinical pathologic features and HSD11B2 were analysed via Wilcoxon signed-rank test and logistic regression. Clinicopathologic characteristics associated with overall survival in melanoma patients were calculated using Cox regression and the Kaplan-Meier method. Gene Set Enrichment Analysis (GSEA) and gene co-association of HSD11B2 were performed using TCGA data set. Results: Reduced HSD11B2 expression was significantly lower in melanoma patients compared to normal patients (p value = 3.004e-122) and also associated with lower survivability. low HSD11B2 expression in melanoma was also significantly associated with cancer stages T (p value = 0.002) and N (p value < 0.001) and age (p value = 0.003). Genes TFCP2L1, PRR15L, ATP6V1B1, C9orf152, AC009948.1, AL391244.1, WDCP, HNRNPCP2 and GTF2E1 were all shown to be co-associated with changes in HSD1B2 expression. Multiple signalling pathway including cytosolic DNA sensing pathway, JAK STAT signalling pathway, NOD like receptor signalling pathway, T cell receptor signalling pathway and Toll like receptor signalling pathway were differentially enriched in low HSD11B2 expression phenotype. Conclusion: Our study revealed that HSD11B2 expression is closely associated with melanoma development and age, as well as multiple cancer related genes and pathways, thus highlighting HSD11B2 as a potential therapeutic marker of melanoma.

scholarly journals Identification of a five-miRNA signature predicting survival in cutaneous melanoma cancer patients

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7831 ◽  
Author(s):  
Tao Lu ◽  
Shuang Chen ◽  
Le Qu ◽  
Yunlin Wang ◽  
Hong-duo Chen ◽  
...  
Keyword(s):  
Cutaneous Melanoma ◽  
Target Genes ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Microarray Dataset ◽  
Bioinformatic Analysis ◽  
The Cancer Genome Atlas ◽  
Mirna Signature ◽  
Sequencing Data ◽  
Melanoma Patients

Background Cutaneous melanoma (CM) is the deadliest form of skin cancer. Numerous studies have revealed that microRNAs (miRNAs) are expressed abnormally in melanoma tissues. Our work aimed to assess multiple miRNAs using bioinformatic analysis in order to predict the prognoses of cutaneous melanoma patients. Methods The microarray dataset GSE35579 was downloaded from the Gene Expression Omnibus (GEO) database to detect the differential expression of miRNAs (DEMs), including 41 melanoma (primary and metastatic) tissues and 11 benign nevi. Clinical information and miRNA sequencing data of cutaneous melanoma tissues were downloaded from the Cancer Genome Atlas database (TCGA) to assess the prognostic values of DEMs. Additionally, the target genes of DEMs were anticipated using miRanda, miRmap, TargetScan, and PicTar. Finally, functional analysis was performed using selected target genes on the Annotation, Visualization and Integrated Discovery (DAVID) website. Results After performing bioinformatic analysis, a total of 185 DEMs were identified: 80 upregulated miRNAs and 105 downregulated miRNAs. A five-miRNA (miR-25, miR-204, miR-211, miR-510, miR-513c) signature was discovered to be a potential significant prognostic biomarker of cutaneous melanoma when using the Kaplan–Meier survival method (P = 0.001). Univariate and multivariate Cox regression analyses showed that the five-miRNA signature could be an independent prognostic marker (HR = 0.605, P = 0.006) in cutaneous melanoma patients. Biological pathway analysis indicated that the target genes may be involved in PI3K-Akt pathways, ubiquitin-mediated proteolysis, and focal adhesion. Conclusion The identified five-miRNA signature may serve as a prognostic biomarker, or as a potential therapeutic target, in cutaneous melanoma patients.

scholarly journals Who’s Driving? Switch of Drivers in Immunotherapy-Treated Progressing Sinonasal Melanoma

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2725
Author(s):  
Sandra N. Freiberger ◽  
Patrick Turko ◽  
Martin Hüllner ◽  
Reinhard Dummer ◽  
Grégoire B. Morand ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Cutaneous Melanoma ◽  
Primary Tumor ◽  
Progressive Disease ◽  
Causal Relation ◽  
Resistance Mechanisms ◽  
Mucosal Melanoma ◽  
Recurrent Event ◽  
Driver Mutations ◽  
Molecular Testing

Mucosal melanoma can be driven by various driver mutations in genes such as NRAS, KIT, or KRAS. However, some cases present with only weak drivers, or lacking known oncogenic drivers, suggesting immunotherapy over targeted therapy. While resistance mechanisms to immunotherapy in cutaneous melanoma have been uncovered, including alterations in JAK1/2, B2M, or STK11, a switch of oncogenic drivers under immunotherapy has not yet been observed. We report three cases of metastatic sinonasal melanoma that switched oncogenic drivers from KRAS, KIT, or no driver to NRAS during or after immunotherapy, thereby showing progressive disease. One of the cases presented with three spatially separate driver mutations in the primary tumor, whereas the NRAS clone persisted under immunotherapy. In comparison, three different control cases receiving radiotherapy only did not show a change of the detectable molecular drivers in their respective recurrences or metastases. In summary, these data provide an important rationale for longitudinal molecular testing, based on evidence for an unforeseen recurrent event of molecular driver switch to NRAS in progressing sinonasal melanoma. These findings provide the basis for further studies on a potential causal relation of emerging NRAS mutant clones and immunotherapy.

scholarly journals The Integrative Analysis Identifies Three Cancer Subtypes and Stemness Features in Cutaneous Melanoma

2021 ◽  
Vol 7 ◽  
Author(s):  
Xiaoran Wang ◽  
Qi Wan ◽  
Lin Jin ◽  
Chengxiu Liu ◽  
Chang Liu ◽  
...  
Keyword(s):  
Survival Time ◽  
Cutaneous Melanoma ◽  
Immune Therapy ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Recursive Feature Elimination ◽  
Support Vector ◽  
Tumor Purity ◽  
Melanoma Patients ◽  
Immune Score

Background: With the growing uncovering of drug resistance in melanoma treatment, personalized cancer therapy and cancer stem cells are potential therapeutic targets for this aggressive skin cancer.Methods: Multi-omics data of cutaneous melanoma were obtained from The Cancer Genome Atlas (TCGA) database. Then, these melanoma patients were classified into different subgroups by performing "CancerSubtypes" method. The differences of stemness indices (mRNAsi and mDNAsi) and tumor microenvironment indices (immune score, stromal score, and tumor purity) among subtypes were investigated. Moreover, the Least Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) algorithms were performed to identify a cancer cell stemness feature, and the likelihood of immuno/chemotherapeutic response was further explored.Results: Totally, 3 specific subtypes of melanoma with different survival outcomes were identified from TCGA. We found subtype 2 of melanoma with the higher immune score and stromal score and lower mRNAsi and tumor purity score, which has the best survival time than the other subtypes. By performing Kaplan–Meier survival analysis, we found that mRNAsi was significantly associated with the overall survival time of melanomas in subtype 2. Correlation analysis indicated surprising associations between stemness indices and subsets of tumor-infiltrating immune cells. Besides, we developed and validated a prognostic stemness-related genes feature that can divide melanoma patients into high- and low-risk subgroups by applying risk score system. The high-risk group has a significantly shorter survival time than the low-risk subgroup, which is more sensitive to CTLA-4 immune therapy. Finally, 16 compounds were screened out in the Connectivity Map database which may be potential therapeutic drugs for melanomas.Conclusion: Thus, our finding provides a new framework for classification and finds some potential targets for the treatment of melanoma.

scholarly journals Prognostic Value and Immunological Characteristics of a Novel RNA Binding Protein Signature in Cutaneous Melanoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Jun Tian ◽  
Chongzhi Ma ◽  
Li Yang ◽  
Yang Sun ◽  
Yuan Zhang
Keyword(s):  
High Risk ◽  
Cutaneous Melanoma ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Risk Group ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Prognostic Signature ◽  
Potential Biomarker ◽  
Melanoma Patients

BackgroundThe existing studies indicate that RNA binding proteins (RBPs) are closely correlated with the genesis and development of cancers. However, the role of RBPs in cutaneous melanoma remains largely unknown. Therefore, the present study aims to establish a reliable prognostic signature based on RBPs to distinguish cutaneous melanoma patients with different prognoses and investigate the immune infiltration of patients.MethodsAfter screening RBPs from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, Cox and least absolute shrinkage and selection operator (LASSO) regression analysis were then used to establish a prediction model. The relationship between the signature and the abundance of immune cell types, the tumor microenvironment (TME), immune-related pathways, and immune checkpoints were also analyzed.ResultsIn total, 7 RBPs were selected to establish the prognostic signature. Patients categorized as a high-risk group demonstrated worse overall survival (OS) rates compared to those of patients categorized as a low-risk group. The signature was validated in an independent external cohort and indicated a promising prognostic ability. Further analysis indicated that the signature wasan independent prognostic indicator in cutaneous melanoma. A nomogram combining risk score and clinicopathological features was then established to evaluate the 3- and 5-year OS in cutaneous melanoma patients. Analyses of immune infiltrating, the TME, immune checkpoint, and drug susceptibility revealed significant differences between the two groups. GSEA analysis revealed that basal cell carcinoma, notch signaling pathway, melanogenesis pathways were enriched in the high-risk group, resulting in poor OS.ConclusionWe established and validated a robust 7-RBP signature that could be a potential biomarker to predict the prognosis and immunotherapy response of cutaneous melanoma patients, which provides new insights into cutaneous melanoma immunotherapeutic strategies.

Whole genome and RNA sequencing reveal the distinct genomic landscape of acral melanoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9589-9589 ◽  
Author(s):  
Yan Kong ◽  
Zhihong Chi ◽  
Lu Si ◽  
Xinan Sheng ◽  
Chuanliang Cui ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Skin Diseases ◽  
Driver Mutations ◽  
Sequencing Data ◽  
Single Nucleotide Variants ◽  
Illumina Hiseq ◽  
Acral Melanoma ◽  
Therapy Strategy ◽  
Spin Column ◽  
Melanoma Patients

9589 Background: Acral melanoma is a common subtype of melanoma in Asians with extremely poor prognosis, and therapy strategy has not been clearly established for acral melanoma. The aim of this study is to perform genomic and RNA profiling of acral melanoma to obtain the comprehensive genomic view of this subtype of melanoma. Methods: Genomic DNA was extracted with Qiagen DNeasy Blood or Tissue Kit . DNA libraries were prepared using a CancerPROTM-P88 BOX library Prep kit and sequencing was performed using the Illumina HiSeq X10. RNA was isolated with Qiagen RNeasy mini-spin column. cDNA was synthesized from total RNA using the SuperScript III first-strand synthesis system . RNA libraries were prepared using the NEBNext Ultra II Directional RNA Library Prep Kit and sequencing was performed using the Illumina HiSeq X10. Results: To obtain a comprehensive genomic and functional genomic view of acral melanoma, we sequenced the genomes of 14 acral melanoma and transcriptomes of 11 of these melanoma samples. We found a new mutation in the V28 codon of BRAF in three patients. Furthermore, we identified recurrent non-synonymous single nucleotide variants in previously described oncogene NRAS, as well as in genes encoding keratin associated proteins (KRTAP4-7, KRTAP4-5) and mucin (MUC2, MUC21). Notably, a recurrent noncoding hotspot mutation was discovered in 4 of 11 cases. By analyzing the RNA sequencing data, we found significant divergence on transcriptome between patients with or without ulcer. In total, we identified 201 genes were significantly up-regulated and 386 genes significantly down-regulated in acral melanoma patients with ulcer. Differentially expressed genes were enriched in pathways associated with cancers, melanogenesis, cell death signaling, skin diseases, etc. Conclusions: Our study reveals potentially different driver mutations and distinct transcriptome in acral melanoma patients compared with cutaneous melanoma patients and sheds lights to the further personalized medicine for acral melanoma patients.

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