{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:50:31Z","timestamp":1786114231819,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    metabolizes about 20% of commonly used drugs, including tamoxifen, a major hormone therapy for breast cancer. Although the relationship between tamoxifen pharmacokinetics and\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    genotype has been demonstrated, residual variability in drug exposure remains unexplained. Given the high genetic polymorphism of\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    , including copy number variations and hybrid genes, targeted genotyping may fail to capture rare or complex alleles. To explore this limitation, 68 individuals from a cohort of tamoxifen\u2010treated patients were selected based on discordance between\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    genotype determined by a targeted approach and phenotype assessed from pharmacokinetic data, and were analyzed using full\u2010gene next\u2010generation sequencing with in\u2010house panel and bioinformatics pipeline. Full\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    gene sequencing refined genotypes in 41% of patients, and changed metabolizer status in 19%, mainly by detecting common alleles missed by the initial targeted assay. After removing these sources of discrepancy, sequencing improved diplotype assignment in 23.5% and metabolizer status classification in 7.4% of patients, largely driven by the detection of structural variants, with an additional contribution from the rare nonfunctional\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    *62 allele, identified in one patient. In addition, several rare variants or variants of uncertain significance (including\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    *22, *23, *28, p.Ala165Gly. and p.Pro264Thr) were identified and further evaluated using adapted\n                    <jats:italic>in silico<\/jats:italic>\n                    prediction strategies, compared with patients' phenotypes and published\n                    <jats:italic>in vitro<\/jats:italic>\n                    data. Comprehensive\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    sequencing improved gene profiling accuracy in our preselected cohort, while highlighting the remaining challenges of rare variant interpretation in pharmacogenetics\u2010guided therapeutic drug monitoring.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70360","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T13:49:38Z","timestamp":1781790578000},"page":"731-744","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Does Next Generation Sequencing (\n                    <scp>NGS<\/scp>\n                    )\u2010Based\n                    <scp>\n                      <i>CYP2D6<\/i>\n                    <\/scp>\n                    Sequencing Improve Genotype\u2013Phenotype Concordance in Tamoxifen\u2010Treated Patients?"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9524-2608","authenticated-orcid":false,"given":"Jeanne","family":"Petit","sequence":"first","affiliation":[{"name":"Univ Toulouse Oncopole\u2010Claudius Regaud, IUCT\u2010Oncopole, Inserm, CRCT  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Plenecassagnes","sequence":"additional","affiliation":[{"name":"Bioinformatics Department Oncopole Claudius Regaud, IUCT\u2010Oncopole  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelie","family":"Brice","sequence":"additional","affiliation":[{"name":"Univ Toulouse Oncopole\u2010Claudius Regaud, IUCT\u2010Oncopole, Inserm, CRCT  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Dalenc","sequence":"additional","affiliation":[{"name":"Univ Toulouse Oncopole\u2010Claudius Regaud, IUCT\u2010Oncopole, Inserm, CRCT  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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9886-412X","authenticated-orcid":false,"given":"Fabienne","family":"Thomas","sequence":"additional","affiliation":[{"name":"Univ Toulouse Oncopole\u2010Claudius Regaud, IUCT\u2010Oncopole, Inserm, CRCT  Toulouse 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