文章：

胸腺瘤患者对培美曲塞单药治疗产生卓越反应的全外显子测序

Whole Exome Sequencing of Thymoma Patients Exhibiting Exceptional Responses to Pemetrexed Monotherapy

原文发布日期：8 August 2023

DOI: 10.3390/cancers15164018

类型: Article

开放获取: 是

英文摘要：

Background: Pemetrexed is used for the chemotherapy of advanced thymoma. Exceptional responses of thymoma to pemetrexed treatment are not frequently observed. The underlying genetic mechanism of the exceptional responses remains unclear. We used whole-exome sequencing to explore the specific genomic aberrations that lead to an extreme and durable response. Methods: Whole-exome sequencing using NovaSeq6000 (150 bp paired-end sequencing) was performed on nine formalin-fixed paraffin-embedded tissues from patients with advanced thymomas treated with pemetrexed (two exceptional responders and seven typical responders). Results: We identified 284 somatic single-nucleotide variants (SNVs; 272 missense, 8 missense/splice-site, 3 stop-gain, and 1 stop-gain/splice-site), 34 insertions and deletions (Indels; 33 frameshift and one splice region), and 21 copy number variations (CNVs; 15 gains and six losses). No difference in the number of SNVs variants and distribution of deleterious Indels was observed between the exceptional and typical responders. Interestingly, arm-level chromosomal CNVs (15 gains and six losses) were detected in four patients, including an exceptional responder. The highest number of arm-level CNVs was observed in an exceptional responder. Conclusion: Exceptional responders to pemetrexed for metastatic thymomas may be characterized by arm-level CNVs. Further, whole-genome and RNA sequencing studies should be performed.

摘要翻译： 

背景：培美曲塞常用于晚期胸腺瘤的化疗。胸腺瘤对培美曲塞治疗产生异常应答的情况并不常见，其背后的遗传机制尚不明确。本研究采用全外显子测序技术，旨在探索导致极端且持久治疗应答的特异性基因组变异。方法：对九例接受培美曲塞治疗的晚期胸腺瘤患者的福尔马林固定石蜡包埋组织（包括两例异常应答者和七例典型应答者）进行全外显子测序（使用NovaSeq6000平台，150 bp双端测序）。结果：共检测到284个体细胞单核苷酸变异（SNVs；其中272个错义突变、8个错义/剪接位点复合突变、3个无义突变及1个无义/剪接位点复合突变），34个插入缺失突变（Indels；其中33个移码突变和1个剪接区突变），以及21个拷贝数变异（CNVs；包括15个扩增和6个缺失）。异常应答者与典型应答者在SNVs数量及有害Indels的分布上未见显著差异。值得注意的是，在四例患者（含一例异常应答者）中检测到臂水平染色体CNVs（15个扩增和6个缺失），其中异常应答者表现出最高数量的臂水平CNVs。结论：转移性胸腺瘤对培美曲塞的异常应答可能与臂水平CNVs相关，后续需开展全基因组及RNA测序研究加以验证。

原文链接：

Whole Exome Sequencing of Thymoma Patients Exhibiting Exceptional Responses to Pemetrexed Monotherapy