{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T16:30:29Z","timestamp":1793205029455,"version":"4.5.0"},"reference-count":42,"publisher":"American Society for Clinical Investigation","issue":"17","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["R35CA294022"],"award-info":[{"award-number":["R35CA294022"]}]},{"name":"The Pacific Northwest Prostate Cancer SPORE","award":["P50CA97186"],"award-info":[{"award-number":["P50CA97186"]}]},{"name":"Program Project Grant","award":["PO1CA163227"],"award-info":[{"award-number":["PO1CA163227"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,8]]},"abstract":"<jats:p>BACKGROUND. Loss of the Y chromosome (LOY) is a frequent event in male tumors and has been linked to cancer progression. However, the degree of mosaic LOY (mLOY) within normal tissues from men with or without cancer remains uncharacterized.<\/jats:p>\n                  <jats:p>METHODS. Here we used a FISH-based assay targeting X- and Y-chromosome centromeres to perform a pan-organ analysis of mLOY in 1,000 male tissue samples from 405 individuals representing 11 organs. Automated image processing generated a quantitative FISH-based mLOY score (YchrFISH) that we validated against a transcriptomic surrogate of Y-chromosome dosage from RNA-seq data.<\/jats:p>\n                  <jats:p>\n                    RESULTS. mLOY burden varied by tumor type, with highest degree in colorectal carcinoma. Across tissue groups, YchrFISH scores declined progressively from normal tissues of cancer-free men to histologically normal tissues adjacent to cancer and carcinoma (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001). Paired analyses confirmed consistently greater mLOY in malignant compared with tumor-adjacent histologically normal tissue in different organs. Spatially resolved RNA-seq maps of bladders removed for cancer demonstrated a transcriptional gradient of Y-chromosome loss from normal urothelium through intraepithelial neoplasia to invasive carcinoma.\n                  <\/jats:p>\n                  <jats:p>CONCLUSION. mLOY gradients exist across histologically normal and malignant tissues, consistent with the concept of field cancerization. Our findings support epithelial mLOY as a biomarker of early malignant transformation and, to our knowledge, a previously unrecognized hallmark of male oncogenesis.<\/jats:p>\n                  <jats:p>FUNDING. NIH grants R35CA294022, P01CA163227, and P50CA97186 (the Pacific Northwest Prostate Cancer SPORE) and the Institute for Prostate Cancer Research.<\/jats:p>","DOI":"10.1172\/jci.insight.201996","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:01:06Z","timestamp":1788804066000},"source":"Crossref","is-referenced-by-count":3,"title":["Human Y chromosome pan-organ mapping reveals progressive mosaic loss from normal to cancer"],"prefix":"10.1172","volume":"11","author":[{"given":"Arkadiusz","family":"Gertych","sequence":"first","affiliation":[{"name":"Department of Surgery,"},{"name":"Department of Pathology and Laboratory Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, and"},{"name":"Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Vail","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. 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