<i>MAPK</i> Pathway and <i>TERT</i> Promoter Gene Mutation Pattern and Its Prognostic Value in Melanoma Patients: A Retrospective Study of 2,793 Cases

Bai, Xue; Kong, Yan; Chen, Zhihong; Sheng, Xinan; Cui, Chuanliang; Wang, Xuan; Mao, Lili; Tang, Bixia; Li, Siming; Lian, Bin; Yan, Xieqiao; Zhou, Li; Dai, Jie; Guo, Jun; Si, Lu

doi:10.1158/1078-0432.ccr-17-0980

Cited by 73 publications

(73 citation statements)

References 41 publications

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“…The BRAF mutation rates in cases of AM reported in previous Asian studies were much higher than reported herein (Table S10). In contrast, the NRAS mutation rates in AMs reported in this study were similar to those described in other Asian studies. Compared with the overall results from Asian populations, KIT and KRAS mutations were found to be more prevalent in AMs in our study population .…”

Section: Discussionsupporting

confidence: 90%

Genetic alterations in primary melanoma in Taiwan

et al. 2019

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Summary Background Acral melanoma (AM) is the most common histopathological subtype of malignant melanoma in Asians. However, differences in the mutational profiles underlying AM and nonacral cutaneous melanoma (NAM) in Asians are not well understood. Objectives To augment the understanding of the prevalence, patterns and associations of various mutations between different subtypes of melanoma. Methods We performed comprehensive genomic profiling of 409 cancer‐associated genes, using next‐generation sequencing, in 66 primary melanomas comprised of 45 AMs and 21 NAMs. Results Most of the AMs (n = 27/45; 60%), but only five of 21 (24%) NAMs, were triple wild‐type (triple‐WT) tumours. Compared with AMs, NAMs exhibited a significantly higher frequency of BRAF mutations. The frequencies of NRAS/KRAS mutations, cell‐cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and gains of receptor tyrosine kinase genes were significantly higher in AMs. Ulceration was found at significantly higher rates in the AMs and NAMs with cell‐cycle aberrations and gains of receptor tyrosine kinase genes. Notably, cell‐cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma‐specific survival in the 66 patients with melanoma and especially in the 45 patients with AM. Multivariate analysis showed that lymph node metastasis and cell‐cycle aberrations were independent prognostic factors of melanoma‐specific survival. Conclusions This study strengthens our understanding of the patterns and clinical associations of oncogenic mutations in AMs and NAMs in Asians. What's already known about this topic? Mutation frequencies of driver genes vary between melanoma subtypes. Acral melanoma is the most common subtype of melanoma in Asians. KIT mutations and copy number variations occur more frequently in the acral subtype of melanoma than in the nonacral subtype What does this study add? NRAS/KRAS mutations, cell‐cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and amplifications of receptor tyrosine kinase genes were significantly enriched in acral melanoma and could be potential targets for treatment. Melanomas with cell‐cycle aberrations and gains in receptor tyrosine kinase genes were significantly more likely to contain ulceration. What is the translational message? Cell‐cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma‐specific survival. These observations should be explored further for future drug development.

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Section: Discussionsupporting

confidence: 90%

Genetic alterations in primary melanoma in Taiwan

et al. 2019

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“…After PCR, PCR products were puri ed using QIAquick (Qiagen), followed by Sanger sequencing (Tianyihuiyuan Company, Beijing, China). The speci c DNA preparation and mutation detection methods were consistent with previous reports [11].…”

Section: Dna Preparation and Mutation Screeningsupporting

confidence: 87%

Gene Mutation Characteristics and Clinical Prognosis of Head and Neck Mucosal Melanoma

Yin¹,

Guo²,

Liu³

et al. 2020

Preprint

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Background: As a highly malignant tumor type, the mucosal type is the second most common pathological subtype in China. In this study, we analyzed the results and clinical data for C-KIT, NRAS, PDGFRA and BRAF genotypes in patients, to explore the characteristics of gene mutation in head and neck mucosal melanoma and the correlation between the four common gene mutation types and prognosis.Methods: C-KIT (exons 9, 11, 13, 17 and 18), NRAS (exons 1 and 2), PDGFRA (exons 12, 14 and 18) and BRAF (exons 11 and 15) were analyzed by PCR amplification and Sanger sequencing in patients. The Chi-squared test, Log rank test and Cox regression model were used to analyze the risk factors. Results: In total, 96 patients were included in the study. 14 (14.58%) patients had the C-KIT mutation, 6 (6.25%) had the BRAF mutation, 23 (23.96%) had the PDGFRA mutation, and 12 (12.50%) had the NRAS mutation. The NRAS mutation (P = 0.037, 95%CI: 1.050–4.572) was an independent factor affecting postoperative distant metastasis. The mutation types of different primary tumor sites were different. The BRAF mutation was more common in the nasopharynx and other sites (P = 0.008), whereas the NRAS mutation was more common in the nasal cavity/sinus (P = 0.043).Conclusion: The specificity of this genotype may have some guiding significance for treatment of patients with head and neck mucosal melanoma, but this study did not find any correlation with survival time, and this needs further analysis with a larger dataset.

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“…On the one hand, BRAF mutations were identified in about 80% benign naevi of various histological types [38], implying a critical role in the initiation of melanoma. On the other hand, BRAF mutations were found more common in melanomas with advanced stages like vertical growth phase, lymph node metastasis, or ulceration [7,39,40], suggesting that BRAF mutations correlated more with melanoma progression. All BRAF variants in our study were identified in patients with lymph node metastasis, which support the later statement that BRAF is important in progression rather than initiation of the melanoma.…”

Section: Discussionmentioning

confidence: 99%

“…e difference in subtypes might indicate a discrepancy of major genetic variation patterns between Asian and Caucasian melanoma patients and could direct to different therapeutic treatments. For example, while BRAF gene mutation is one of the most frequently mutated genes in European and American populations (above 40%) [5,6], only about 25% of Asian patients harbored BRAF alterations [7]. e disparities in subtypes also have been associated with several melanoma predisposition genes.…”

Section: Introductionmentioning

confidence: 99%

Characterizations of Gene Alterations in Melanoma Patients from Chinese Population

Luo

Zhang

Liu

et al. 2020

BioMed Research International

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Melanoma is a human skin malignant tumor with high invasion and poor prognosis. The limited understanding of genomic alterations in melanomas in China impedes the diagnosis and therapeutic strategy selection. We conducted comprehensive genomic profiling of melanomas from 39 primary and metastatic formalin-fixed paraffin-embedded (FFPE) samples from 27 patients in China based on an NGS panel of 223 genes. No significant difference in gene alterations was found between primary and metastasis melanomas. The status of germline mutation, CNV, and somatic mutation in our cohort was quite different from that reported in Western populations. We further delineated the mutation patterns of 4 molecular subgroups (BRAF, RAS, NF1, and Triple-WT) of melanoma in our cohort. BRAF mutations were more frequently identified in melanomas without chromic sun-induced damage (non-CSD), while RAS mutations were more likely observed in acral melanomas. NF1 and Triple-WT subgroups were unbiased between melanomas arising in non-CSD and acral skin. BRAF, RAS, and NF1 mutations were significantly associated with lymph node metastasis or presence of ulceration, implying that these cancer driver genes were independent prognostic factors. In summary, our results suggest that mutational profiles of malignant melanomas in China are significantly different from Western countries, and both gene mutation and amplification play an important role in the development and progression of melanomas.

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MAPK Pathway and TERT Promoter Gene Mutation Pattern and Its Prognostic Value in Melanoma Patients: A Retrospective Study of 2,793 Cases

Cited by 73 publications

References 41 publications

Genetic alterations in primary melanoma in Taiwan

Genetic alterations in primary melanoma in Taiwan

Gene Mutation Characteristics and Clinical Prognosis of Head and Neck Mucosal Melanoma

Characterizations of Gene Alterations in Melanoma Patients from Chinese Population

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