{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T06:18:03Z","timestamp":1788329883162,"version":"build-2803163510"},"reference-count":85,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T00:00:00Z","timestamp":1749254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Johns Hopkins School of Medicine Department of Pathology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Chromoanagenesis is a catastrophic genomic phenomenon involving sudden, extensive rearrangements within one or a few cell cycles. In osteosarcoma, the most prevalent malignant bone tumor in children and adolescents, these events dramatically alter the genomic landscape, frequently disrupting key tumor suppressor genes like TP53 and RB1, amplifying oncogene expression, and propelling tumor progression and evolution. This review elucidates how key chromoanagenic mechanisms, such as chromothripsis and chromoanasynthesis, arise from replication stress and impaired DNA repair pathways, ultimately contributing to genomic instability in osteosarcoma. Chromothripsis features prominently in osteosarcoma, occurring in up to 62% of tumor regions and driving intratumoral heterogeneity through persistent genomic crises. Next-generation sequencing, optical genome mapping, and emerging technologies like single-cell sequencing empower researchers to detect and characterize these complex structural variants, demonstrating how a single catastrophic event can profoundly influence osteosarcoma progression over time. While targeted therapies for osteosarcoma have proven elusive, innovative strategies harnessing comprehensive genomic profiling and patient-derived preclinical models hold promise for uncovering tumor-specific vulnerabilities tied to chromoanagenesis. Ultimately, unraveling how these rapid, large-scale rearrangements fuel osteosarcoma\u2019s aggressive nature will not only refine disease classification and prognosis but also pave the way for novel therapeutic approaches to enhance patient outcomes.<\/jats:p>","DOI":"10.3390\/biom15060833","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T09:13:01Z","timestamp":1749460381000},"page":"833","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Chromoanagenesis in Osteosarcoma"],"prefix":"10.3390","volume":"15","author":[{"given":"Guozhuang","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China"},{"name":"Beijing Key Laboratory of Big Data Innovation and Application for Skeletal Health Medical Care, Beijing 100730, China"},{"name":"Key Laboratory of Big Data for Spinal Deformities, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China"},{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9429-2889","authenticated-orcid":false,"given":"Nan","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Complex Severe and Rare Diseases, Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China"},{"name":"Beijing Key Laboratory of Big Data Innovation and Application for Skeletal Health Medical Care, Beijing 100730, China"},{"name":"Key Laboratory of Big Data for Spinal Deformities, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1993-4087","authenticated-orcid":false,"given":"Jen","family":"Ghabrial","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0317-1385","authenticated-orcid":false,"given":"Victoria","family":"Stinnett","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Klausner","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Morsberger","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patty","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezra","family":"Baraban","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Gross","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2787-1917","authenticated-orcid":false,"given":"Ying S.","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41572-022-00409-y","article-title":"Osteosarcoma","volume":"8","author":"Beird","year":"2022","journal-title":"Nat. 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