使用双靶向 DNA 和 RNA 综合基因组图谱分析面板对非小细胞肺癌进行分子分析。

IF 2.4 Q2 RESPIRATORY SYSTEM

Respiratory investigation Pub Date : 2024-08-09 DOI:10.1016/j.resinv.2024.07.018

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引用次数: 0

摘要

背景：癌症基因组综合分析测试最近已用于临床，以指导最佳治疗。目前获批的检测使用组织或血浆样本中的 DNA 来分析几百个基因。RNA面板是DNA面板的补充，可检测融合和外显子跳越：2017年4月至2022年3月期间，我们使用Todai OncoPanel分析了非小细胞肺癌样本，这是一种针对DNA和RNA的匹配肿瘤/正常配对面板。公开的基因组数据于2022/11/3从癌症基因组学和先进治疗中心数据库下载：分析了60个非小细胞肺癌（NSCLC）样本。通过DNA面板，32个样本（53%）出现TP53功能缺失突变。在腺癌中，17 个样本（33%）有表皮生长因子受体激活突变，6 个样本（12%）有 ERBB2 激活突变。此外，还检测到一个 BRCA1 和一个 BRCA2 致病性种系变异。通过 RNA 面板，共检测到 11 个融合基因，全部出现在腺癌中。其中，EML4-ALK和KIF5B-RET各从一个样本中检测到，另外9个都是致病性未知的新型融合基因。此外，60 份 NSCLC 样本中有 4 份（7%）存在 MET 第 14 号外显子缺失。对癌症基因组学和高级治疗中心数据库的分析发现，在1514个NSCLC样本中有37个MET第14外显子剪接位点突变（2%，P = 0.039）：结论：使用Todai OncoPanel分析NSCLC发现了许多可用于治疗的靶点。结论：使用 Todai OncoPanel 分析 NSCLC 发现了许多可用于治疗的靶点，其 RNA 面板可高灵敏度地检测 MET 第 14 号外显子跳接。

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Molecular analysis of non-small cell lung cancer using a dual-targeted DNA and RNA comprehensive genomic profiling panel

Background

Comprehensive cancer genomic profiling tests have recently been used clinically to guide optimal treatment. Currently approved tests use DNA from tissue or plasma samples to analyze a few hundred genes. RNA panels complement DNA panels to detect fusion and exon skipping.

Methods

Between April 2017 and March 2022, we analyzed non-small cell lung cancer samples using Todai OncoPanel, a matched tumor/normal pair panel targeting both DNA and RNA. Publicly available genomic data was downloaded from the Center for Cancer Genomics and Advanced Therapeutics database on 2022/11/3.

Results

Sixty non-small cell lung cancer (NSCLC) samples were analyzed. With the DNA panel, 32 samples (53%) had TP53 loss-of-function mutations. Among adenocarcinoma, 17 (33%) had EGFR activating mutations, and 6 (12%) had ERBB2 activating mutations. One BRCA1 and one BRCA2 pathogenic germline variant were also detected. With the RNA panel, 11 fusion genes were detected, all in adenocarcinoma. Specifically, EML4-ALK and KIF5B-RET were detected from one sample each, and 9 others were all novel fusions with unknown pathogenicity. In addition, 4 of 60 (7%) NSCLC samples harbored MET exon 14 skipping. Analysis of the Center for Cancer Genomics and Advanced Therapeutics database found 37 MET exon 14 splice site mutations in 1514 NSCLC samples (2%, p = 0.039).