Heritable defects in telomere and mitotic function selectively predispose to sarcomas.
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| Title: | Heritable defects in telomere and mitotic function selectively predispose to sarcomas. |
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| Authors: | Ballinger, Mandy L., Pattnaik, Swetansu, Mundra, Piyushkumar A., Zaheed, Milita, Rath, Emma, Priestley, Peter, Baber, Jonathan, Ray-Coquard, Isabelle, Isambert, Nicholas, Causeret, Sylvain, van der Graaf, Winette T. A., Puri, Ajay, Duffaud, Florence, Le Cesne, Axel, Seddon, Beatrice, Chandrasekar, Coonoor, Schiffman, Joshua D., Brohl, Andrew S., James, Paul A., Kurtz, Jean-Emmanuel |
| Source: | Science (pre-March 2025). 1/20/2023, Vol. 379 Issue 6629, p253-260. 8p. 4 Color Photographs, 2 Charts. |
| Subjects: | Telomeres, Cancer susceptibility, Sarcoma, Mesenchymal stem cells, Phenotypes, Centrosomes |
| Abstract: | Cancer genetics has to date focused on epithelial malignancies, identifying multiple histotype-specific pathways underlying cancer susceptibility. Sarcomas are rare malignancies predominantly derived from embryonic mesoderm. To identify pathways specific to mesenchymal cancers, we performed whole-genome germline sequencing on 1644 sporadic cases and 3205 matched healthy elderly controls. Using an extreme phenotype design, a combined rare-variant burden and ontologic analysis identified two sarcoma-specific pathways involved in mitotic and telomere functions. Variants in centrosome genes are linked to malignant peripheral nerve sheath and gastrointestinal stromal tumors, whereas heritable defects in the shelterin complex link susceptibility to sarcoma, melanoma, and thyroid cancers. These studies indicate a specific role for heritable defects in mitotic and telomere biology in risk of sarcomas. [ABSTRACT FROM AUTHOR] |
| Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | Cancer genetics has to date focused on epithelial malignancies, identifying multiple histotype-specific pathways underlying cancer susceptibility. Sarcomas are rare malignancies predominantly derived from embryonic mesoderm. To identify pathways specific to mesenchymal cancers, we performed whole-genome germline sequencing on 1644 sporadic cases and 3205 matched healthy elderly controls. Using an extreme phenotype design, a combined rare-variant burden and ontologic analysis identified two sarcoma-specific pathways involved in mitotic and telomere functions. Variants in centrosome genes are linked to malignant peripheral nerve sheath and gastrointestinal stromal tumors, whereas heritable defects in the shelterin complex link susceptibility to sarcoma, melanoma, and thyroid cancers. These studies indicate a specific role for heritable defects in mitotic and telomere biology in risk of sarcomas. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 00368075 |
| DOI: | 10.1126/science.abj4784 |
