{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T06:04:26Z","timestamp":1762149866233,"version":"build-2065373602"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Pharmacogenomic testing is rapidly becoming the standard of care in treating pediatric acute lymphoblastic leukemia (ALL). Risk classification of ALL can be performed through whole transcriptome sequencing (WTS) of diagnostic tumor samples. We evaluated the feasibility of inferring germline pharmacogenomic genotypes from the tumor transcriptome in ALL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Transcriptome and paired tumor-germline genome sequencing data were collected from clinical testing at St. Jude Children\u2019s Research Hospital. Genotypes for pharmacogenes that are actionable for medications used in the management of pediatric ALL (\n                      <jats:italic toggle=\"yes\">TPMT, NUDT15<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">G6PD<\/jats:italic>\n                      ) were determined using a rule-based algorithm from transcriptome data. WTS-derived genotype calls were compared with germline genotypes obtained from whole genome sequencing (WGS) and clinical genotyping assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 650 patients with ALL, 36 (5.5%) patients had somatic copy number loss on chromosomes 6, 13, or X, where\n                      <jats:italic toggle=\"yes\">TPMT<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">NUDT15<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">G6PD<\/jats:italic>\n                      are located, respectively. For the remaining 614 patients, WTS provided thiopurine dosing guidance by calling both\n                      <jats:italic toggle=\"yes\">TPMT<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">NUDT15<\/jats:italic>\n                      diplotypes in 545 patients (83.8%). For\n                      <jats:italic toggle=\"yes\">G6PD<\/jats:italic>\n                      , accurate genotyping was called for 367 male patients. We observed a greater than 99% concordance between tumor WTS and germline WGS diplotypes for all three genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The leukemia transcriptome can be used to provide accurate genotyping calls for select germline pharmacogenes actionable in the treatment of pediatric ALL.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/fpc.0000000000000576","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T10:01:23Z","timestamp":1758794483000},"page":"1-8","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Inferring germline pharmacogenomics from tumor transcriptome"],"prefix":"10.1097","volume":"36","author":[{"given":"Wenjian","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Applied Bioinformatics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffery M.","family":"Klco","sequence":"additional","affiliation":[{"name":"Department of Pathology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim E.","family":"Nichols","sequence":"additional","affiliation":[{"name":"Department of Oncology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sima","family":"Jeha","sequence":"additional","affiliation":[{"name":"Department of Oncology"},{"name":"Department of Global Pediatric Medicine, St. Jude Children\u2019s Research Hospital, Memphis, Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroto","family":"Inaba","sequence":"additional","affiliation":[{"name":"Department of Oncology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching-Hon","family":"Pui","sequence":"additional","affiliation":[{"name":"Department of Pathology"},{"name":"Department of Oncology"},{"name":"Department of Global Pediatric Medicine, St. Jude Children\u2019s Research Hospital, Memphis, Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nickhill","family":"Bhakta","sequence":"additional","affiliation":[{"name":"Department of Oncology"},{"name":"Department of Global Pediatric Medicine, St. Jude Children\u2019s Research Hospital, Memphis, Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Broeckel","sequence":"additional","affiliation":[{"name":"RPRD Diagnostics LLC, Milwaukee, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun J.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences"},{"name":"Department of Oncology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyrine E.","family":"Haidar","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"R1-20251103","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0140-6736(19)31276-0","article-title":"Pharmacogenomics.","volume":"394","author":"Roden","year":"2019","journal-title":"Lancet (London, England)"},{"key":"R2-20251103","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/cpt.1651","article-title":"The clinical pharmacogenetics implementation consortium: 10 years later.","volume":"107","author":"Relling","year":"2020","journal-title":"Clin Pharmacol Ther"},{"key":"R3-20251103","doi-asserted-by":"crossref","first-page":"2730","DOI":"10.1056\/NEJMoa0900386","article-title":"Treating childhood acute lymphoblastic 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Oncol"},{"key":"R13-20251103","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1158\/2159-8290.CD-20-1631","article-title":"Genomes for kids: the scope of pathogenic mutations in pediatric cancer revealed by comprehensive DNA and RNA sequencing.","volume":"11","author":"Newman","year":"2021","journal-title":"Cancer Discov"},{"key":"R14-20251103","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1158\/2159-8290.CD-20-1230","article-title":"St. Jude Cloud: a pediatric cancer genomic data-sharing ecosystem.","volume":"11","author":"McLeod","year":"2021","journal-title":"Cancer Discov"},{"key":"R15-20251103","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1101\/gr.078212.108","article-title":"Mapping short DNA sequencing reads and calling variants using mapping quality scores.","volume":"18","author":"Li","year":"2008","journal-title":"Genome 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