Comprehensive molecular findings in primary malignant melanoma of the esophagus: A multicenter study

IF 3.9 3区 医学 Q2 CELL BIOLOGY Pigment Cell & Melanoma Research Pub Date : 2023-12-29 DOI:10.1111/pcmr.13157
Ling Deng, Hai-Yun Wang, Chun-Fang Hu, Xiao-Yun Liu, Kuntai Jiang, Juan-Juan Yong, Xiao-Yan Wu, Kai-Hua Guo, Fang Wang
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Abstract

Primary malignant melanoma of the esophagus (PMME) is an extremely rare but highly aggressive malignancy with a poor prognosis. Due to the scarcity of driver gene alterations, there is a need for more clinical data to comprehensively depict its molecular alterations. This study reviewed 26 PMME cases from three medical centers. Hybrid capture-based targeted sequencing of 295 and 1021 genes was performed in 14 and 12 cases, respectively. We found that PMME patients had a relatively low tumor mutation burden (median, 2.88 mutations per Mb) and were simultaneously accompanied by mutations in genes such as KIT (6/26, 23%), TP53 (6/26, 23%), SF3B1 (4/26, 15%), and NRAS (3/26, 12%). KIT, NRAS, and BRAF were mutually exclusive, and SF3B1 co-occurred with KIT mutation and amplification. The most common pathways affected were the mitogen-activated protein kinases and DNA damage response (DDR) pathways. Stage IV was a risk factor for both progression-free survival (hazard ratio [HR] = 5.14, 95% confidence interval [CI] = 1.32–19.91) and overall survival (OS), HR = 4.33, 95% CI = 1.22–15.30). Treatment with immune-checkpoint inhibitors (ICIs) was an independent factor for favorable OS (HR = 0.10, 95% CI = 0.01–0.91). Overall, PMME is a complex malignancy with diverse gene alterations, especially with harboring DDR alterations for potentially response from ICIs.

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食管原发性恶性黑色素瘤的综合分子研究结果:一项多中心研究。
食管原发性恶性黑色素瘤(PMME)是一种极为罕见但侵袭性极强的恶性肿瘤,预后极差。由于缺乏驱动基因的改变,因此需要更多的临床数据来全面描述其分子改变。本研究回顾了来自三个医疗中心的26例PMME病例。分别对14例和12例患者的295个和1021个基因进行了基于混合捕获的靶向测序。我们发现,PMME 患者的肿瘤突变负荷相对较低(中位数为每 Mb 2.88 个突变),同时伴有 KIT(6/26,23%)、TP53(6/26,23%)、SF3B1(4/26,15%)和 NRAS(3/26,12%)等基因的突变。KIT、NRAS和BRAF相互排斥,SF3B1与KIT突变和扩增同时存在。最常见的受影响途径是丝裂原活化蛋白激酶和DNA损伤应答(DDR)途径。IV期是无进展生存期(危险比[HR] = 5.14,95%置信区间[CI] = 1.32-19.91)和总生存期(OS)(HR = 4.33,95%置信区间[CI] = 1.22-15.30)的危险因素。接受免疫检查点抑制剂(ICIs)治疗是获得良好OS的独立因素(HR = 0.10,95% CI = 0.01-0.91)。总之,PMME是一种复杂的恶性肿瘤,存在多种基因改变,尤其是DDR改变,可能对ICIs产生反应。
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来源期刊
Pigment Cell & Melanoma Research
Pigment Cell & Melanoma Research 医学-皮肤病学
CiteScore
8.90
自引率
2.30%
发文量
54
审稿时长
6-12 weeks
期刊介绍: Pigment Cell & Melanoma Researchpublishes manuscripts on all aspects of pigment cells including development, cell and molecular biology, genetics, diseases of pigment cells including melanoma. Papers that provide insights into the causes and progression of melanoma including the process of metastasis and invasion, proliferation, senescence, apoptosis or gene regulation are especially welcome, as are papers that use the melanocyte system to answer questions of general biological relevance. Papers that are purely descriptive or make only minor advances to our knowledge of pigment cells or melanoma in particular are not suitable for this journal. Keywords Pigment Cell & Melanoma Research, cell biology, melatonin, biochemistry, chemistry, comparative biology, dermatology, developmental biology, genetics, hormones, intracellular signalling, melanoma, molecular biology, ocular and extracutaneous melanin, pharmacology, photobiology, physics, pigmentary disorders
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