Michelle Garlin Politis, Mahesh Mansukhani, Benjamin O Herzberg, Lanyi N Chen, Mark Stoopler, Maelle Saliba, Markus Siegelin, Zhe Zhu, Joshua Sonett, Brian S Henick, Simon K Cheng, Swarnali Acharyya, Catherine A Shu, Michael L Miller, Benjamin Izar, Helen Fernandes, Susan Hsiao, Anjali Saqi
{"title":"原发性肺癌中枢神经系统转移：RNA融合检测和早期与晚期转移的意义。","authors":"Michelle Garlin Politis, Mahesh Mansukhani, Benjamin O Herzberg, Lanyi N Chen, Mark Stoopler, Maelle Saliba, Markus Siegelin, Zhe Zhu, Joshua Sonett, Brian S Henick, Simon K Cheng, Swarnali Acharyya, Catherine A Shu, Michael L Miller, Benjamin Izar, Helen Fernandes, Susan Hsiao, Anjali Saqi","doi":"10.3390/jpm15050181","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background/Objectives:</b> While the genomic landscape of primary lung carcinomas is well characterized, there is a relative scarcity of fusion data on corresponding central nervous system (CNS) metastases. This study aimed to elucidate the molecular profiles of CNS metastases to (1) assess the significance of a combined DNA-reflex RNA fusion testing approach and (2) compare the mutational landscape between patients who present initially [early (≤2 months)] with CNS metastases and those who develop CNS metastases thereafter [late (>2 months)]. <b>Methods</b>: We performed a retrospective search of CNS metastases of adenocarcinoma of probable lung origin interrogated by targeted DNA-reflex RNA next-generation sequencing (NGS). The DNA NGS panel included the driver mutations <i>EGFR</i>, <i>BRAF</i>, <i>KRAS</i>, <i>MET</i>, and <i>ERBB2</i>. RNA NGS included <i>ALK</i>, <i>RET</i>, <i>ROS1</i>, and <i>MET</i>. Additionally, mutational profiles were examined between those with early versus late CNS metastases. <b>Results:</b> Of the 58 patients, 44 (75.9%) had mutations or alterations, including 34 identified by DNA NGS [<i>EGFR</i> (<i>n</i> = 17; 50.0%), <i>KRAS</i> (<i>n</i> = 15; 44.1%), <i>MET</i> (<i>n</i> = 2; 5.9%)] and 10/24 by RNA NGS [<i>ALK</i> (<i>n</i> = 7; 70%), <i>MET</i> (<i>n</i> = 2; 20%), <i>ROS1</i> (<i>n</i> = 1; 10%)]. Of all patients, 32 (55%) presented with early and 26 (45%) with late CNS metastases. Although patients with early metastases had worse survival compared to those with late metastases (<i>p</i> < 0.001), there were no statistically significant differences in the mutational profiles between the two cohorts. <b>Conclusions</b>: A significant proportion of CNS metastases without driver mutations identified by DNA NGS had targetable alterations identified by RNA NGS (10/24, 41.7%). In summary, a combined DNA with reflex RNA fusion testing approach plays a significant role in detecting and potentially managing CNS metastases. Comprehensive prospective studies are essential to elucidate the differences between early and late CNS metastases.</p>","PeriodicalId":16722,"journal":{"name":"Journal of Personalized Medicine","volume":"15 5","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112828/pdf/","citationCount":"0","resultStr":"{\"title\":\"Central Nervous System Metastases from Primary Lung Carcinoma: Significance of RNA Fusion Testing and Early Versus Late Metastases.\",\"authors\":\"Michelle Garlin Politis, Mahesh Mansukhani, Benjamin O Herzberg, Lanyi N Chen, Mark Stoopler, Maelle Saliba, Markus Siegelin, Zhe Zhu, Joshua Sonett, Brian S Henick, Simon K Cheng, Swarnali Acharyya, Catherine A Shu, Michael L Miller, Benjamin Izar, Helen Fernandes, Susan Hsiao, Anjali Saqi\",\"doi\":\"10.3390/jpm15050181\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Background/Objectives:</b> While the genomic landscape of primary lung carcinomas is well characterized, there is a relative scarcity of fusion data on corresponding central nervous system (CNS) metastases. This study aimed to elucidate the molecular profiles of CNS metastases to (1) assess the significance of a combined DNA-reflex RNA fusion testing approach and (2) compare the mutational landscape between patients who present initially [early (≤2 months)] with CNS metastases and those who develop CNS metastases thereafter [late (>2 months)]. <b>Methods</b>: We performed a retrospective search of CNS metastases of adenocarcinoma of probable lung origin interrogated by targeted DNA-reflex RNA next-generation sequencing (NGS). The DNA NGS panel included the driver mutations <i>EGFR</i>, <i>BRAF</i>, <i>KRAS</i>, <i>MET</i>, and <i>ERBB2</i>. RNA NGS included <i>ALK</i>, <i>RET</i>, <i>ROS1</i>, and <i>MET</i>. Additionally, mutational profiles were examined between those with early versus late CNS metastases. <b>Results:</b> Of the 58 patients, 44 (75.9%) had mutations or alterations, including 34 identified by DNA NGS [<i>EGFR</i> (<i>n</i> = 17; 50.0%), <i>KRAS</i> (<i>n</i> = 15; 44.1%), <i>MET</i> (<i>n</i> = 2; 5.9%)] and 10/24 by RNA NGS [<i>ALK</i> (<i>n</i> = 7; 70%), <i>MET</i> (<i>n</i> = 2; 20%), <i>ROS1</i> (<i>n</i> = 1; 10%)]. Of all patients, 32 (55%) presented with early and 26 (45%) with late CNS metastases. Although patients with early metastases had worse survival compared to those with late metastases (<i>p</i> < 0.001), there were no statistically significant differences in the mutational profiles between the two cohorts. <b>Conclusions</b>: A significant proportion of CNS metastases without driver mutations identified by DNA NGS had targetable alterations identified by RNA NGS (10/24, 41.7%). In summary, a combined DNA with reflex RNA fusion testing approach plays a significant role in detecting and potentially managing CNS metastases. Comprehensive prospective studies are essential to elucidate the differences between early and late CNS metastases.</p>\",\"PeriodicalId\":16722,\"journal\":{\"name\":\"Journal of Personalized Medicine\",\"volume\":\"15 5\",\"pages\":\"\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112828/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Personalized Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3390/jpm15050181\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"HEALTH CARE SCIENCES & SERVICES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Personalized Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/jpm15050181","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEALTH CARE SCIENCES & SERVICES","Score":null,"Total":0}
Central Nervous System Metastases from Primary Lung Carcinoma: Significance of RNA Fusion Testing and Early Versus Late Metastases.
Background/Objectives: While the genomic landscape of primary lung carcinomas is well characterized, there is a relative scarcity of fusion data on corresponding central nervous system (CNS) metastases. This study aimed to elucidate the molecular profiles of CNS metastases to (1) assess the significance of a combined DNA-reflex RNA fusion testing approach and (2) compare the mutational landscape between patients who present initially [early (≤2 months)] with CNS metastases and those who develop CNS metastases thereafter [late (>2 months)]. Methods: We performed a retrospective search of CNS metastases of adenocarcinoma of probable lung origin interrogated by targeted DNA-reflex RNA next-generation sequencing (NGS). The DNA NGS panel included the driver mutations EGFR, BRAF, KRAS, MET, and ERBB2. RNA NGS included ALK, RET, ROS1, and MET. Additionally, mutational profiles were examined between those with early versus late CNS metastases. Results: Of the 58 patients, 44 (75.9%) had mutations or alterations, including 34 identified by DNA NGS [EGFR (n = 17; 50.0%), KRAS (n = 15; 44.1%), MET (n = 2; 5.9%)] and 10/24 by RNA NGS [ALK (n = 7; 70%), MET (n = 2; 20%), ROS1 (n = 1; 10%)]. Of all patients, 32 (55%) presented with early and 26 (45%) with late CNS metastases. Although patients with early metastases had worse survival compared to those with late metastases (p < 0.001), there were no statistically significant differences in the mutational profiles between the two cohorts. Conclusions: A significant proportion of CNS metastases without driver mutations identified by DNA NGS had targetable alterations identified by RNA NGS (10/24, 41.7%). In summary, a combined DNA with reflex RNA fusion testing approach plays a significant role in detecting and potentially managing CNS metastases. Comprehensive prospective studies are essential to elucidate the differences between early and late CNS metastases.
期刊介绍：
Journal of Personalized Medicine (JPM; ISSN 2075-4426) is an international, open access journal aimed at bringing all aspects of personalized medicine to one platform. JPM publishes cutting edge, innovative preclinical and translational scientific research and technologies related to personalized medicine (e.g., pharmacogenomics/proteomics, systems biology). JPM recognizes that personalized medicine—the assessment of genetic, environmental and host factors that cause variability of individuals—is a challenging, transdisciplinary topic that requires discussions from a range of experts. For a comprehensive perspective of personalized medicine, JPM aims to integrate expertise from the molecular and translational sciences, therapeutics and diagnostics, as well as discussions of regulatory, social, ethical and policy aspects. We provide a forum to bring together academic and clinical researchers, biotechnology, diagnostic and pharmaceutical companies, health professionals, regulatory and ethical experts, and government and regulatory authorities.
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