{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T20:45:08Z","timestamp":1782765908989,"version":"3.54.5"},"reference-count":62,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"6","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Rare cancers are molecularly heterogeneous and lack robust clinical evidence to guide treatment. Whether cancer driver gene expression is governed by tumor lineage or specific somatic alterations\u2014and whether this distinction carries clinical relevance\u2014remains poorly characterized, particularly in Asian populations. This study aimed to determine the relative contributions of tumor lineage and DNA mutations to RNA expression of cancer driver genes and to evaluate the clinical implications of genomic alteration status in Asian patients with rare cancers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      DNA and RNA were extracted from formalin-fixed paraffin-embedded tumor samples obtained through the MASTER KEY Asia research network. Next-generation sequencing was performed to evaluate genomic alterations and gene expression profiles. RNA expression of cancer driver genes was quantified as TPM\n                      <jats:italic toggle=\"yes\">Z<\/jats:italic>\n                      scores. Elastic net regression with 10-fold cross-validation assessed the relative contributions of tumor lineage and DNA mutations to RNA expression, and findings were independently replicated in another cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Integrated DNA and RNA data were available for 128 patients. Tumor lineage was the predominant determinant of RNA expression in 17 of 27 cancer driver genes (63%), whereas\n                      <jats:italic toggle=\"yes\">ERBB2<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">MDM2<\/jats:italic>\n                      demonstrated genomic-predominant regulation, replicated across both cohorts. Alterations in\n                      <jats:italic toggle=\"yes\">ERBB2<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">ARID1A<\/jats:italic>\n                      were associated with a lower frequency of disease progression compared with patients without either alteration (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .01), independently of\n                      <jats:italic toggle=\"yes\">ERBB2<\/jats:italic>\n                      RNA expression. Functional subclassification of\n                      <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                      revealed that gain-of-function mutations were associated with higher rates of disease progression (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .007) and shorter progression-free survival than loss-of-function variants (hazard ratio, 2.355 [95% CI, 1.086 to 5.105];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .029). Tumor mutational burden was not associated with treatment response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      These findings demonstrate that genomic alteration status, including\n                      <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                      functional subclassification, provides clinically meaningful information beyond transcriptional profiling alone, supporting integrative genomics and transcriptomics analysis for precision oncology in rare cancers.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-00907","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T19:59:11Z","timestamp":1782763151000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Integrating DNA Mutations and RNA Expression of Cancer Driver Genes in Asian Rare Cancers: A Pan-Cancer Analysis"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8568-7897","authenticated-orcid":true,"given":"Kathleen Yasmin","family":"de Almeida","sequence":"first","affiliation":[{"name":"Department of International Clinical Development, National Cancer Center Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Severino B.","family":"Imasa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, St Luke's Medical Center, Quezon, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei Jye","family":"Voon","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Oncology and Palliative Care, Hospital Umum Sarawak (Sarawak General Hospital), Kuching Sarawak, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwoei Fen","family":"Soo Hoo","sequence":"additional","affiliation":[{"name":"Consultant Clinical Oncologist and Training Lead, Penang General Hospital, Pulau Pinang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom Wei-Wu","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhana","family":"Yusak","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy and Oncology, National Cancer Institute, Putrajaya, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rangasamy","family":"Ramachandran","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, University Malaya, Kuala Lumpur, 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