{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T12:52:45Z","timestamp":1782391965042,"version":"3.54.5"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alterations of the Y chromosome are frequent events in solid tumors, yet their biological and clinical significance remains incompletely understood. In colorectal cancer (CRC), recent studies have suggested context\u2010dependent roles of Y\u2010linked genes in tumor progression, while the impact of tumor\u2010associated loss of the Y chromosome (LoY) in metastatic disease has not been clearly established.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively analyzed primary tumor samples from 91 male patients with metastatic CRC treated at a single institution. Tumor LoY status was assessed using a droplet digital PCR\u2013based assay. Associations between LoY, clinicopathological characteristics,\n                      <jats:italic>KRAS\/BRAF<\/jats:italic>\n                      mutation status, and patient outcomes, including progression\u2010free survival (PFS) and overall survival (OS), were evaluated. Exploratory analyses of TCGA\u2010COAD\/READ data were performed using chromosome Y copy\u2010number segment data, mutation data, and survival information.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Tumor LoY was detected in 46 cases (50.5%) and was more frequent in rectal cancers (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.038). LoY was not associated with age, microsatellite instability status,\n                      <jats:italic>KRAS<\/jats:italic>\n                      or\n                      <jats:italic>BRAF<\/jats:italic>\n                      mutations. While PFS did not differ according to LoY status, OS was longer in patients with LoY\u2010positive tumors (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.046). In multivariable analysis, LoY showed a non\u2010significant trend toward improved OS (HR\u2009=\u20090.52, 95% CI: 0.25\u20131.10;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.07). In exploratory TCGA analyses, chromosome Y copy\u2010number signal did not significantly differ between colon and rectal cancers, but lower chromosome Y signal was associated with worse OS, particularly in TCGA\u2010COAD after adjustment for age and\n                      <jats:italic>KRAS<\/jats:italic>\n                      \/\n                      <jats:italic>BRAF<\/jats:italic>\n                      status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>LoY is a frequent chromosomal alteration in metastatic CRC and appears enriched in rectal primary tumors in our cohort. Its association with clinical outcome may depend on disease stage, molecular background, and analytical methodology. These findings support further investigation of Y chromosome loss as a context\u2010dependent biomarker in CRC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/gcc.70147","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T04:16:32Z","timestamp":1781496992000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Primary Tumor\u2010Associated Loss of the Y Chromosome and Clinical Outcome in Metastatic Colorectal Cancer"],"prefix":"10.1002","volume":"65","author":[{"given":"Ana\u00eblle","family":"Isnard","sequence":"first","affiliation":[{"name":"CHU Bordeaux, Tumor Biology and Tumor Bank Laboratory  Pessac France"},{"name":"BRIC (BoRdeaux Institute of Oncology), INSERM, University of Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Decraecker","sequence":"additional","affiliation":[{"name":"BRIC (BoRdeaux Institute of Oncology), INSERM, University of Bordeaux  Bordeaux France"},{"name":"Oncology Unit Haut L\u00e9v\u00eaque Hospital, University Hospital Center of Bordeaux  Pessac France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Fernandez","sequence":"additional","affiliation":[{"name":"BRIC (BoRdeaux Institute of Oncology), INSERM, University of Bordeaux  Bordeaux France"},{"name":"CHU Bordeaux Colorectal Digestive Surgery Department  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Smith","sequence":"additional","affiliation":[{"name":"Oncology Unit Haut L\u00e9v\u00eaque Hospital, University Hospital Center of Bordeaux  Pessac France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Dubus","sequence":"additional","affiliation":[{"name":"CHU Bordeaux, Tumor Biology and Tumor Bank Laboratory  Pessac France"},{"name":"BRIC (BoRdeaux Institute of Oncology), INSERM, University of Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Dabernat","sequence":"additional","affiliation":[{"name":"BRIC (BoRdeaux Institute of Oncology), INSERM, University of Bordeaux  Bordeaux France"},{"name":"CHU Bordeaux, Biochemistry Laboratory  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7943-8800","authenticated-orcid":false,"given":"Olivier","family":"Mansier","sequence":"additional","affiliation":[{"name":"CHU Bordeaux, Hematology Laboratory  Bordeaux France"},{"name":"Biology of Cardiovascular Diseases INSERM, University of Bordeaux  Pessac France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3238-5251","authenticated-orcid":false,"given":"Samuel","family":"Amintas","sequence":"additional","affiliation":[{"name":"CHU Bordeaux, Tumor Biology and Tumor Bank Laboratory  Pessac France"},{"name":"BRIC 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