K.T. Tan’s research while affiliated with Taipei Medical University and other places

黑色素瘤是一种危及生命的皮肤癌。2015 年,全世界约 351,800 人患有该疾病。肢端黑色素瘤发生于无毛肢端皮肤(手掌、脚底和甲床),而且与紫外线辐射(如阳光)无关,这与其他黑色素瘤类型(非肢端黑色素瘤)不同。 这项研究由中国台湾的研究人员完成,旨在查明亚洲人某些基因中的哪些突变(异常)导致肢端黑色素瘤和非肢端黑色素瘤。这称为“基因组分析”,其让科学家了解与个人或细胞类型相关的遗传信息以及基因相互作用的方式。这种分析可使用一种称为下一代测序的基因检测进行。 作者在 66 例黑色素瘤中对 409 个癌症相关的基因进行了全面基因组测序(包括 45 例肢端黑色素瘤和 21 例非肢端黑色素瘤)。 作者发现,非肢端黑色素瘤显示 BRAF 突变频率显著高于肢端黑色素瘤。同时,其他改变的频率(NRAS/KRAS 突变、细胞周期畸变、抗细胞凋亡通路改变和受体酪氨酸激酶基因增益)在肢端黑色素瘤中显著更高。 研究发现在肢端黑色素瘤和具有细胞周期畸变和受体酪氨酸激酶基因增益的非肢端黑色素瘤中,溃疡(黑色素瘤表面皮肤损坏)的发生率显著更高。值得注意的是,在所有 66 例黑色素瘤患者中,细胞周期畸变和抗细胞凋亡通路改变均与更低的生存率相关,尤其是 45 例肢端黑色素瘤患者。 本研究加强了我们对亚洲人肢端和非肢端黑色素瘤基因突变模式和影响的了解。研究表明,除了称为免疫疗法的治疗外,肢端黑色素瘤患者可能受益于 NRAS/KRAS 突变、细胞周期畸变、受体酪氨酸激酶基因增益和抗细胞凋亡通路靶向治疗,这种可能性在未来需要研究。 本摘要涉及研究:在台湾原发性黑色素瘤中的基因变异。

Melanoma is a life‐threatening type of skin cancer. It affected about 351,800 people worldwide in 2015. Acral melanoma occurs on non‐hairy acral skin (palms, soles, and nail beds) and is not thought to be linked to ultraviolet radiation (e.g. from the sun), unlike other melanoma types (non‐acral melanoma). This study, conducted by researchers based in Taiwan, aimed to find out which mutations (abnormalities) in certain genes underly acral melanoma and non‐acral melanoma in Asians. This is known as ‘genomic profiling’, and allows scientists to find out about the genetic information related to a person or cell type and the way genes interact with each other. This profiling can be done using a type of genetic testing called next‐generation sequencing. The authors performed comprehensive genomic profiling of 409 cancer‐associated genes in 66 melanomas, comprised of 45 acral melanomas and 21 non‐acral melanomas. The authors found that the non‐acral melanomas showed a significantly higher frequency of a type of mutation called BRAF mutations than the acral melanomas. Meanwhile, the frequencies of other alterations (NRAS/KRAS mutations, cell cycle aberrations, anti‐apoptosis pathway alterations, and receptor tyrosine kinase gene gains) were significantly higher in the acral melanomas. Ulceration, in which the skin on the surface of the melanoma breaks down, was found at significantly higher rates in the acral melanomas and non‐acral melanomas with cell cycle aberrations and receptor tyrosine kinase gene gains. Notably, cell cycle aberrations and anti‐apoptosis pathway alterations were associated with a lower rate of survival in all 66 melanoma patients, and especially in the 45 acral melanoma patients. This study strengthens our understanding of the patterns and repercussions of gene mutations in acral and non‐acral melanoma in Asians. The study revealed that, in addition to treatments called immunotherapies, acral melanoma patients might benefit from treatments that target NRAS/KRAS mutations, cell cycle aberrations, receptor tyrosine kinase gains, and anti‐apoptosis pathways, a possibility which warrants study in the future. This is a summary of the study: Genetic alterations in primary melanoma in Taiwan.

Background: Acral melanoma (AM) is the most common histopathological subtype of malignant melanoma in Asians. However, differences in the mutational profiles underlying AM and non-acral 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 (27/45, 60%), but only 5 of 21 (23·8%) NAMs were the Triple wild-type (Triple-WT) tumors. Compared with the AMs, the NAMs exhibited a significantly higher frequency of BRAF mutation. Meanwhile, the frequencies of NRAS/KRAS mutations, cell cycle aberrations, copy number gains of BIRC2/3/5, and gains of receptor tyrosine kinase genes were significantly higher in the 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 of BIRC2/3/5 were significantly associated with poor melanoma-specific survival in all 66 melanoma patients and especially in the 45 AM patients. Furthermore, a multivariate analysis showed that lymph node metastasis and cell cycle aberrations were independent prognostic factors for melanoma-specific survival. Conclusions: This study strengthens our understanding of the patterns and clinical associations of oncogenic mutations in AMs and NAMs in Asians. This article is protected by copyright. All rights reserved.