{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T13:16:28Z","timestamp":1771334188693,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100032442","name":"Gene Solutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100032442","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Comprehensive genomic profiling (CGP) is a time\u2010 and tissue\u2010 efficient method to help guide precision oncology. To enhance the clinical utility of CGP, we investigated the performance of a novel strategy integrating tumor DNA and mRNA profiling, together with liquid biopsy ctDNA monitoring.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Genomic DNA and mRNA simultaneously extracted from 604 archived tissue samples of 12 cancer types were used. Tumor DNA was subjected to targeted sequencing using a 504\u2010gene panel with high\u2010density probes (HDP), and shallow whole genome sequencing to profile genomic biomarkers. mRNA transcriptome profiling was performed to further capture fusion variants, and to predict tissue of origin (TOO) using our ensemble model OriCUP, an algorithm trained on 9889 samples and independently validated on 731 samples. In a cohort of 55 metastatic lung cancer patients, longitudinal plasma ctDNA was analyzed using a hybrid tumor\u2010informed and tumor\u2010agnostic approach to predict progression\u2010free survival (PFS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among all biomarkers, DNA sequencing using HDP achieved higher sensitivity than the standard panel design to identify copy number variations at chromosome\u2010, gene\u2010, and exon\u2010 levels. The detection rate of fusion variants using DNA sequencing alone was 20% lower than mRNA sequencing in reference samples, while the combination of both methods was essential to maximize fusion detection in clinical FFPE samples. For TOO, our OriCup model achieved prediction accuracy of 87.7% for primary tumors and 81.4% for metastatic tumors. In 55 lung cancer patients, ctDNA profiling identified additional 11.5% tumor\u2010agnostic actionable and resistance mutations. Patients having more than 50% ctDNA decrease from baseline were classified as molecular responders and showed significantly longer PFS than those classified as molecular non\u2010responders (HR\u2009=\u20099.42, 95% CI: 3.33\u201326.67,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001, 12\u2010month PFS: 95.5% vs. 31.7%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Comprehensive genomic and transcriptomic profiling could reliably unveil genetic details not provided by DNA\u2010only CGP. The integration of ctDNA detection further helped detect tumor\u2010agnostic mutations and monitor treatment response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71465","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T02:55:38Z","timestamp":1765248938000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tumor Genomic and Transcriptomic Analysis Integrated With Liquid Biopsy\n                    <scp>ctDNA<\/scp>\n                    Monitoring: Analytical Validation and Clinical Insights"],"prefix":"10.1002","volume":"14","author":[{"given":"Nam H. B.","family":"Tran","sequence":"first","affiliation":[{"name":"Medical Genetics Institute  Ho Chi Minh City Vietnam"},{"name":"Gene Solutions  Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thien\u2010Phuc Hoang","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute  Ho Chi Minh City Vietnam"},{"name":"Gene Solutions  Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinh Quang","family":"Bui","sequence":"additional","affiliation":[{"name":"Hanoi Oncology Hospital  Hanoi Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vu Thuong","family":"Le","sequence":"additional","affiliation":[{"name":"University Medical Center of HCMC  Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trong Khoa","family":"Mai","sequence":"additional","affiliation":[{"name":"Bach Mai Hospital  Hanoi Vietnam"},{"name":"Ha Noi Medical University  Hanoi Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Van\u2010Anh","family":"Nguyen Hoang","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute  Ho Chi Minh City Vietnam"},{"name":"Gene Solutions  Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tien Anh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute  Ho Chi Minh City Vietnam"},{"name":"Gene Solutions  Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minh\u2010Duc","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute  Ho Chi Minh City Vietnam"},{"name":"Gene Solutions  Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ha\u2010Hieu","family":"Pham","sequence":"additional","affiliation":[{"name":"Gene Solutions  Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tho Thi Le","family":"Vo","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute  Ho Chi Minh City Vietnam"},{"name":"Gene Solutions  Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"My T. T.","family":"Ngo","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute  Ho Chi Minh City Vietnam"},{"name":"Gene Solutions  Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Du Quyen","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute  Ho Chi Minh City Vietnam"},{"name":"Gene Solutions  Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duy Sinh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute  Ho Chi Minh City Vietnam"},{"name":"Gene Solutions  Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoai\u2010Nghia","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute  Ho Chi Minh City Vietnam"},{"name":"Gene Solutions  Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minh\u2010Duy","family":"Phan","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute  Ho Chi Minh City Vietnam"},{"name":"Gene Solutions  Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoa","family":"Giang","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute  Ho Chi Minh City Vietnam"},{"name":"Gene Solutions  Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6362-8554","authenticated-orcid":false,"given":"Lan N.","family":"Tu","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute  Ho Chi Minh City Vietnam"},{"name":"Gene Solutions  Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-023-02228-x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1369\/0022155420945050"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2020.11.005"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.4643"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-05227-2"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.05.520"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0546-8"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature23306"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/OA-24-00084"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2024.1334808"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.789659"},{"key":"e_1_2_9_13_1","article-title":"Combination of BRCA Deep Targeted Sequencing and Shallow Whole Genome Sequencing to Detect Homologous Recombination Deficiency in Ovarian Cancer","author":"Nguyen T. 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