دورية أكاديمية

Sequential genomic analysis using a multisample/multiplatform approach to better define rhabdomyosarcoma progression and relapse

التفاصيل البيبلوغرافية
العنوان: Sequential genomic analysis using a multisample/multiplatform approach to better define rhabdomyosarcoma progression and relapse
المؤلفون: de Traux de Wardin, Henry, Dermawan, Josephine K., Merlin, Marie-Sophie, Wexler, Leonard H., Orbach, Daniel, Vanoli, Fabio, Schleiermacher, Gudrun, Geoerger, Birgit, Ballet, Stelly, Guillemot, Delphine, Frouin, Eléonore, Cyrille, Stacy, Delattre, Olivier, Pierron, Gaelle, Antonescu, Cristina R.
المصدر: npj Precision Oncology ; volume 7, issue 1 ; ISSN 2397-768X
بيانات النشر: Springer Science and Business Media LLC
سنة النشر: 2023
مصطلحات موضوعية: Cancer Research, Oncology
الوصف: The genomic spectrum of rhabdomyosarcoma (RMS) progression from primary to relapse is not fully understood. In this pilot study, we explore the sensitivity of various targeted and whole-genome NGS platforms in order to assess the best genomic approach of using liquid biopsy in future prospective clinical trials. Moreover, we investigate 35 paired primary/relapsed RMS from two contributing institutions, 18 fusion-positive (FP-RMS) and 17 fusion-negative RMS (FN-RMS) by either targeted DNA or whole exome sequencing (WES). In 10 cases, circulating tumor DNA (ctDNA) from multiple timepoints through clinical care and progression was analyzed for feasibility of liquid biopsy in monitoring treatment response/relapse. ctDNA alterations were evaluated using a targeted 36-gene custom RMS panel at high coverage for single-nucleotide variation and fusion detection, and a shallow whole-genome sequencing for copy number variation. FP-RMS have a stable genome with relapse, with common secondary alterations CDKN2A/B , MYCN, and CDK4 present at diagnosis and impacting survival. FP-RMS lacking major secondary events at baseline acquire recurrent MYCN and AKT1 alterations. FN-RMS acquire a higher number of new alterations, most commonly SMARCA2 missense mutations. ctDNA analyses detect pathognomonic variants in all RMS patients within our collection at diagnosis, regardless of type of alterations, and confirmed at relapse in 86% of FP-RMS and 100% FN-RMS. Moreover, a higher number of fusion reads is detected with increased disease burden and at relapse in patients following a fatal outcome. These results underscore patterns of tumor progression and provide rationale for using liquid biopsy to monitor treatment response.
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1038/s41698-023-00445-1
الإتاحة: https://doi.org/10.1038/s41698-023-00445-1Test
https://www.nature.com/articles/s41698-023-00445-1.pdfTest
https://www.nature.com/articles/s41698-023-00445-1Test
حقوق: https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test
رقم الانضمام: edsbas.5CC07169
قاعدة البيانات: BASE