{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T18:47:40Z","timestamp":1782067660927,"version":"3.54.5"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>International guidelines suggest prophylactic anticoagulation for patients with cancer at high risk of venous thromboembolism (VTE). Here, we evaluated whether tumor whole-genome sequencing data may improve the selection of high-risk patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>In a pan-cancer cohort of 3087 patients, associations of candidate clinical predictors, the germline extended 297-single nucleotide polymorphism polygenic risk score, tumor mutational characteristics, and somatic tumor mutations with VTE were estimated by calculating hazard ratios (HRs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      During 12-month follow-up, 237 (7.7%) developed VTE. The germline extended 297-single nucleotide polymorphism score was associated with VTE (HR per point increase, 2.11 [95% CI, 1.45\u20133.06]), as well as the total number of somatic structural variants (HR per 1000 increase, 1.21 [95% CI, 1.07\u20131.37]) and 129 somatic mutations (unadjusted\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.05), including\n                      <jats:italic toggle=\"yes\">POLR2E<\/jats:italic>\n                      (HR, 3.34 [95% CI, 1.68\u20136.97]),\n                      <jats:italic toggle=\"yes\">PALM<\/jats:italic>\n                      (HR, 3.73 [95% CI, 1.74\u20137.99]),\n                      <jats:italic toggle=\"yes\">TBX22<\/jats:italic>\n                      (T-box Transcription Factor 22; HR, 2.47 [95% CI, 1.40\u20134.35]), and\n                      <jats:italic toggle=\"yes\">ELANE<\/jats:italic>\n                      (HR, 3.22 [95% CI, 1.51\u20136.87]). To further explore the potential of tumor whole-genome sequencing, prediction models were constructed including selected clinical predictors only (model 1), clinical predictors and germline variants (model 2), and the combination of clinical predictors, germline variants, and 14 top discriminating somatic mutations (model 3). The optimism corrected concordance index was 0.66 (95% CI, 0.62\u20130.69) for model 1, 0.67 (95% CI, 0.62\u20130.72) for model 2, and 0.77 (95% CI, 0.72\u20130.81) for model 3. This was significantly higher than that of the currently endorsed clinical Khorana VTE risk score (concordance index, 0.55 [95% CI, 0.51\u20130.59];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.005).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>These data indicate that tumor whole-genome sequencing may improve VTE prediction by clinical risk scores. Validation studies to confirm these findings are needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circgen.124.005182","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T09:00:33Z","timestamp":1775811633000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor Whole-Genome Sequencing for Prediction of Venous Thromboembolism in Patients With Metastasized Solid Cancer"],"prefix":"10.1161","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6902-3425","authenticated-orcid":true,"given":"Frits I.","family":"Mulder","sequence":"first","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam UMC Location University of Amsterdam, the Netherlands (F.I.M., N.A.M.G., R.J.v.G., T.F.v.H., V.H., H.R.B., P.W.K., N.v.E.)."},{"name":"Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, the Netherlands (F.I.M., N.A.M.G., R.J.G., T.F.H., V.H., H.R.B., P.W.K., N.v.E.)."},{"name":"Department of Internal Medicine, Tergooi MC, Hilversum, the Netherlands (F.I.M., N.A.M.G., P.W.K., N.v.E.)."},{"name":"Department of Medical Oncology, Amsterdam UMC Location Vrije Universiteit Amsterdam, the Netherlands (F.I.M., H.W.M.v.L., M. Labots)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1426-3170","authenticated-orcid":true,"given":"Noori A.M.","family":"Guman","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam UMC Location University of Amsterdam, the Netherlands (F.I.M., N.A.M.G., R.J.v.G., T.F.v.H., V.H., H.R.B., P.W.K., N.v.E.)."},{"name":"Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, the Netherlands (F.I.M., N.A.M.G., R.J.G., T.F.H., V.H., H.R.B., P.W.K., N.v.E.)."},{"name":"Department of Internal Medicine, Tergooi MC, Hilversum, the Netherlands (F.I.M., N.A.M.G., P.W.K., N.v.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7767-7923","authenticated-orcid":true,"given":"Job","family":"van Riet","sequence":"additional","affiliation":[{"name":"Division of AI in Oncology, German Cancer Research Ctr DKFZ, Heidelberg, Germany (J.v.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1818-3928","authenticated-orcid":true,"given":"Roos J.","family":"van Geffen","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam UMC Location University of Amsterdam, the Netherlands (F.I.M., N.A.M.G., R.J.v.G., T.F.v.H., V.H., H.R.B., P.W.K., N.v.E.)."},{"name":"Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, the Netherlands (F.I.M., N.A.M.G., R.J.G., T.F.H., V.H., H.R.B., P.W.K., N.v.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8358-2426","authenticated-orcid":true,"given":"Thijs F.","family":"van Haaps","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam UMC Location University of Amsterdam, the Netherlands (F.I.M., N.A.M.G., R.J.v.G., T.F.v.H., V.H., H.R.B., P.W.K., N.v.E.)."},{"name":"Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, the Netherlands (F.I.M., N.A.M.G., R.J.G., T.F.H., V.H., H.R.B., P.W.K., N.v.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2317-6645","authenticated-orcid":true,"given":"Vahram","family":"Hovsepjan","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam UMC Location University of Amsterdam, the Netherlands (F.I.M., N.A.M.G., R.J.v.G., T.F.v.H., V.H., H.R.B., P.W.K., N.v.E.)."},{"name":"Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, the Netherlands (F.I.M., N.A.M.G., R.J.G., T.F.H., V.H., H.R.B., P.W.K., N.v.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1274-5643","authenticated-orcid":true,"given":"Hanneke W.M.","family":"van Laarhoven","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Amsterdam UMC Location Vrije Universiteit Amsterdam, the Netherlands (F.I.M., H.W.M.v.L., M. 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