Chromoanagenesis in Osteosarcoma
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 tum...
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MDPI AG
2025-06-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/15/6/833 |
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| author | Guozhuang Li Nan Wu Jen Ghabrial Victoria Stinnett Melanie Klausner Laura Morsberger Patty Long Ezra Baraban John M. Gross Ying S. Zou |
| author_facet | Guozhuang Li Nan Wu Jen Ghabrial Victoria Stinnett Melanie Klausner Laura Morsberger Patty Long Ezra Baraban John M. Gross Ying S. Zou |
| author_sort | Guozhuang Li |
| collection | DOAJ |
| description | 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 <i>TP53</i> and <i>RB1</i>, 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’s aggressive nature will not only refine disease classification and prognosis but also pave the way for novel therapeutic approaches to enhance patient outcomes. |
| format | Article |
| id | doaj-art-9febbfc9aeaf4967b2ec9ff5a89c1d23 |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-9febbfc9aeaf4967b2ec9ff5a89c1d232025-08-20T03:27:05ZengMDPI AGBiomolecules2218-273X2025-06-0115683310.3390/biom15060833Chromoanagenesis in OsteosarcomaGuozhuang Li0Nan Wu1Jen Ghabrial2Victoria Stinnett3Melanie Klausner4Laura Morsberger5Patty Long6Ezra Baraban7John M. Gross8Ying S. Zou9State 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, ChinaState 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, ChinaDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USAChromoanagenesis 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 <i>TP53</i> and <i>RB1</i>, 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’s aggressive nature will not only refine disease classification and prognosis but also pave the way for novel therapeutic approaches to enhance patient outcomes.https://www.mdpi.com/2218-273X/15/6/833chromoanagenesisosteosarcomastructural variantchromothripsischromoanasynthesiscopy number variant |
| spellingShingle | Guozhuang Li Nan Wu Jen Ghabrial Victoria Stinnett Melanie Klausner Laura Morsberger Patty Long Ezra Baraban John M. Gross Ying S. Zou Chromoanagenesis in Osteosarcoma Biomolecules chromoanagenesis osteosarcoma structural variant chromothripsis chromoanasynthesis copy number variant |
| title | Chromoanagenesis in Osteosarcoma |
| title_full | Chromoanagenesis in Osteosarcoma |
| title_fullStr | Chromoanagenesis in Osteosarcoma |
| title_full_unstemmed | Chromoanagenesis in Osteosarcoma |
| title_short | Chromoanagenesis in Osteosarcoma |
| title_sort | chromoanagenesis in osteosarcoma |
| topic | chromoanagenesis osteosarcoma structural variant chromothripsis chromoanasynthesis copy number variant |
| url | https://www.mdpi.com/2218-273X/15/6/833 |
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