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https://hdl.handle.net/2440/138044
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Type: | Journal article |
Title: | Heritable defects in telomere and mitotic function selectively predispose to sarcomas |
Author: | Ballinger, M.L. Pattnaik, S. Mundra, P.A. Zaheed, M. Rath, E. Priestley, P. Baber, J. Ray-Coquard, I. Isambert, N. Causeret, S. van der Graaf, W.T.A. Puri, A. Duffaud, F. Le Cesne, A. Seddon, B. Chandrasekar, C. Schiffman, J.D. Brohl, A.S. James, P.A. Kurtz, J.-E. et al. |
Citation: | Science, 2023; 379(6629):253-260 |
Publisher: | American Association for the Advancement of Science (AAAS) |
Issue Date: | 2023 |
ISSN: | 0036-8075 1095-9203 |
Statement of Responsibility: | Mandy L. Ballinger ... Shyamsundar Ravishankar ... the International Sarcoma Kindred Study ... et al. |
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. |
Keywords: | French Exome Project Consortium International Sarcoma Kindred Study Germ Cells Telomere Humans Sarcoma Melanoma Genetic Predisposition to Disease Mitosis Germ-Line Mutation Genetic Variation Shelterin Complex |
Rights: | © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works |
DOI: | 10.1126/science.abj4784 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1004017 http://purl.org/au-research/grants/nhmrc/1081477 http://purl.org/au-research/grants/nhmrc/1104364 http://purl.org/au-research/grants/nhmrc/1139071 http://purl.org/au-research/grants/nhmrc/1121474 |
Published version: | http://dx.doi.org/10.1126/science.abj4784 |
Appears in Collections: | Genetics publications |
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