{"title":"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。","authors":"","doi":"10.1016/j.resinv.2024.07.018","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>Sixty non-small cell lung cancer (NSCLC) samples were analyzed. With the DNA panel, 32 samples (53%) had <em>TP53</em> loss-of-function mutations. Among adenocarcinoma, 17 (33%) had <em>EGFR</em> activating mutations, and 6 (12%) had <em>ERBB2</em> activating mutations. One <em>BRCA1</em> and one <em>BRCA2</em> pathogenic germline variant were also detected. With the RNA panel, 11 fusion genes were detected, all in adenocarcinoma. Specifically, <em>EML4-ALK</em> and <em>KIF5B-RET</em> 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 <em>MET</em> 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).</p></div><div><h3>Conclusions</h3><p>Analysis of NSCLC with Todai OncoPanel detected many druggable targets. Its RNA panel may detect <em>MET</em> exon 14 skipping with high sensitivity.</p></div>","PeriodicalId":20934,"journal":{"name":"Respiratory investigation","volume":null,"pages":null},"PeriodicalIF":2.4000,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2212534524001199/pdfft?md5=ac3b398fcefa1990fed5ee4f12e5d472&pid=1-s2.0-S2212534524001199-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Molecular analysis of non-small cell lung cancer using a dual-targeted DNA and RNA comprehensive genomic profiling panel\",\"authors\":\"\",\"doi\":\"10.1016/j.resinv.2024.07.018\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>Sixty non-small cell lung cancer (NSCLC) samples were analyzed. With the DNA panel, 32 samples (53%) had <em>TP53</em> loss-of-function mutations. Among adenocarcinoma, 17 (33%) had <em>EGFR</em> activating mutations, and 6 (12%) had <em>ERBB2</em> activating mutations. One <em>BRCA1</em> and one <em>BRCA2</em> pathogenic germline variant were also detected. With the RNA panel, 11 fusion genes were detected, all in adenocarcinoma. Specifically, <em>EML4-ALK</em> and <em>KIF5B-RET</em> 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 <em>MET</em> 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).</p></div><div><h3>Conclusions</h3><p>Analysis of NSCLC with Todai OncoPanel detected many druggable targets. Its RNA panel may detect <em>MET</em> exon 14 skipping with high sensitivity.</p></div>\",\"PeriodicalId\":20934,\"journal\":{\"name\":\"Respiratory investigation\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2024-08-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2212534524001199/pdfft?md5=ac3b398fcefa1990fed5ee4f12e5d472&pid=1-s2.0-S2212534524001199-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Respiratory investigation\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2212534524001199\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"RESPIRATORY SYSTEM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Respiratory investigation","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2212534524001199","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
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).
Conclusions
Analysis of NSCLC with Todai OncoPanel detected many druggable targets. Its RNA panel may detect MET exon 14 skipping with high sensitivity.