{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T06:58:16Z","timestamp":1781161096593,"version":"3.54.1"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100008767","name":"Fundaci\u00f3n Agencia Aragonesa para la Investigaci\u00f3n y el Desarrollo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008767","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CB07\/02\/2005"],"award-info":[{"award-number":["CB07\/02\/2005"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/00767"],"award-info":[{"award-number":["PI20\/00767"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI22\/01938"],"award-info":[{"award-number":["PI22\/01938"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["CNS2022\u2010136176"],"award-info":[{"award-number":["CNS2022\u2010136176"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:p>According to the seed and soil hypothesis, the organ specificity of metastasis is not a random process and depends on multiple tumor\u2010intrinsic and microenvironmental factors. In this study, we characterized the mutational landscape of a large cohort of human metastatic samples to investigate whether mutational trends determine metastatic dissemination. Genomic data from nine cancer types (bladder, breast, colorectal, endometrial, melanoma, non\u2010small cell lung cancer, ovarian, pancreatic, and prostate) including 19827 patients were obtained from a pan\u2010cancer study. When restricting the analysis to driver mutations, no robust, recurrent mutational patterns associated with metastatic locations were identified across cancer types. However, when cancer types were analyzed separately, mutational trends associated with specific metastatic locations emerged. Considering the total tumor mutational burden (TMB), central nervous system (CNS)\/brain and lung metastases harbored a higher TMB than other metastatic locations. Since higher TMB in CNS\/brain metastases was also associated with improved prognosis, these findings may be pivotal in refining immunotherapy strategies. Indeed, this observation was confirmed in an independent dataset including patients treated with immunotherapy. In conclusion, our findings suggest that TMB may have greater influence on metastatic organotropism than driver mutational background.<\/jats:p>","DOI":"10.1002\/1878-0261.70200","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T10:52:25Z","timestamp":1769511145000},"page":"1364-1378","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tumor mutational burden as a determinant of metastatic dissemination patterns"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9961-433X","authenticated-orcid":false,"given":"Eduardo","family":"Candeal","sequence":"first","affiliation":[{"name":"Cancer Heterogeneity and Immunomics (CHI) Clinical University Hospital Lozano Blesa, Aragon Health Research Institute (IISA)  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2996-2505","authenticated-orcid":false,"given":"Andrea","family":"Moreno\u2010Manuel","sequence":"additional","affiliation":[{"name":"Cancer Heterogeneity and Immunomics (CHI) Clinical University Hospital Lozano Blesa, Aragon Health Research Institute (IISA)  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3098-6675","authenticated-orcid":false,"given":"Miguel","family":"Salvad\u00f3\u2010Pertierra","sequence":"additional","affiliation":[{"name":"Cancer Heterogeneity and Immunomics (CHI) Clinical University Hospital Lozano Blesa, Aragon Health Research Institute (IISA)  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9854-5097","authenticated-orcid":false,"given":"Cristina","family":"Santos\u2010Vivas","sequence":"additional","affiliation":[{"name":"Medical Oncology Department Catalan Institute of Oncology (ICO) \u2013 ONCOBELL  Barcelona Spain"},{"name":"Consortium for Biomedical Research in Oncology (CIBERONC)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2187-3527","authenticated-orcid":false,"given":"Rebeca","family":"Sanz\u2010Pamplona","sequence":"additional","affiliation":[{"name":"Cancer Heterogeneity and Immunomics (CHI) Clinical University Hospital Lozano Blesa, Aragon Health Research Institute (IISA)  Zaragoza Spain"},{"name":"Aragonese Foundation for Research and Development (ARAID)  Zaragoza Spain"},{"name":"Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010020\u20100134\u2010x"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4871"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1098"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878\u20100261.12024"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08021"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2622"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03799"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010018\u20100145\u20109"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2016.144"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.11.013"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102019\u2010000491"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.01.003"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010018\u20100312\u20108"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201021\u20100327"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(07)60781\u20108"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nox077"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.04.012"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/PO.18.00376"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43856\u2010021\u201000054\u20108"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iotech.2019.11.003"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201014\u20103073"},{"key":"e_1_2_11_23_1","first-page":"33","article-title":"The role of the immune system in brain metastasis","volume":"10","author":"Leibold AT","year":"2019","journal-title":"Curr Neurobiol"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw289"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/2033876"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20101943\u20103"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40268\u2010021\u201000362\u20103"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.566297"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.669398"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326\u20106066.CIR\u201016\u20100325"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.10.019"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.07.001"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2022.103891"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018\u2010019\u20100008\u20108"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.02.009"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007302\u20106"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2015.07.009"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.592"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2014.619"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2013.146"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202013631"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416\u2010021\u201001424\u20108"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.759577"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010024\u201002182\u2010w"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606978"}],"container-title":["Molecular Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1878-0261.70200","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/1878-0261.70200","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1878-0261.70200","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T14:42:17Z","timestamp":1778251337000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/1878-0261.70200"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,27]]},"references-count":44,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/1878-0261.70200"],"URL":"https:\/\/doi.org\/10.1002\/1878-0261.70200","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/1878-0261.70200\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/1878-0261.70200\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/1878-0261.70200\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/1878-0261.70200\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/1878-0261.70200\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/1878-0261.70200\/v2\/response1","asserted-by":"object"}]},"ISSN":["1574-7891","1878-0261"],"issn-type":[{"value":"1574-7891","type":"print"},{"value":"1878-0261","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,27]]},"assertion":[{"value":"2025-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}