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Heritable defects in telomere and mitotic function selectively predispose to sarcomas.
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; Penel, Nicolas; Myklebost, Ola; Meza-Zepeda, Leonardo A; Pickett, Hilda; Kansara, Maya; Waddell, Nicola; Kondrashova, Olga; Pearson, John V; Barbour, Andrew P; Li, Shuai; Nguyen, Tuong L; Fatkin, Diane; Graham, Robert M; Giannoulatou, Eleni; Green, Melissa J; Kaplan, Warren; Ravishankar, Shyamsundar; Copty, Joseph; Powell, Joseph E; Cuppen, Edwin; van Eijk, Kristel; Veldink, Jan; Ahn, Jin-Hee; Kim, Jeong Eun; Randall, R Lor; Tucker, Kathy; Judson, Ian; Sarin, Rajiv; Ludwig, Thomas; Genin, Emmanuelle.
Affiliation
  • Ballinger ML; Garvan Institute of Medical Research, Sydney 2010, Australia.
  • Pattnaik S; St Vincent's Clinical School, University of New South Wales, Sydney 2010, Australia.
  • Mundra PA; Garvan Institute of Medical Research, Sydney 2010, Australia.
  • Zaheed M; St Vincent's Clinical School, University of New South Wales, Sydney 2010, Australia.
  • Rath E; Garvan Institute of Medical Research, Sydney 2010, Australia.
  • Priestley P; St Vincent's Clinical School, University of New South Wales, Sydney 2010, Australia.
  • Baber J; Hereditary Cancer Centre, Prince of Wales Hospital, Sydney 2031, Australia.
  • Ray-Coquard I; Garvan Institute of Medical Research, Sydney 2010, Australia.
  • Isambert N; Hartwig Medical Foundation, 1098 XH Amsterdam, Netherlands.
  • Causeret S; Hartwig Medical Foundation Australia, Sydney 2000, Australia.
  • van der Graaf WTA; Hartwig Medical Foundation, 1098 XH Amsterdam, Netherlands.
  • Puri A; Hartwig Medical Foundation Australia, Sydney 2000, Australia.
  • Duffaud F; Department of Adult Medical Oncology, Centre Leon Berard, University Claude Bernard, 69373 Lyon, France.
  • Le Cesne A; Centre Georges Francois Leclerc, 21000 Dijon, France.
  • Seddon B; Centre Georges Francois Leclerc, 21000 Dijon, France.
  • Chandrasekar C; Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
  • Schiffman JD; Department of Orthopedic Oncology, Tata Memorial Hospital, Mumbai, Maharashtra 400012, India.
  • Brohl AS; la Timone University Hospital, 13005 Marseille, France.
  • James PA; Gustave Roussy, 94805 Villejuif, France.
  • Kurtz JE; Sarcoma Unit, University College Hospital, London NW1 2BU, UK.
  • Penel N; Liverpool University Hospitals NHS Foundation Trust, Liverpool L7 8XP, UK.
  • Myklebost O; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
  • Meza-Zepeda LA; Sarcoma Department, Moffitt Cancer Center, Tampa, FL 33612, USA.
  • Pickett H; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne 3010, Australia.
  • Kansara M; Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne 3000, Australia.
  • Waddell N; Centre Hospitalier Universitaire Hautepierre, 67200 Strasbourg, France.
  • Kondrashova O; Centre Oscar Lambret, 59000 Lille, France.
  • Pearson JV; Western Norway Familial Cancer Centre, Haukeland University Hospital, 5021 Bergen, Norway.
  • Barbour AP; Department of Clinical Science, University of Bergen, 5007 Bergen, Norway.
  • Li S; Institute for Cancer Research, Oslo University Hospital, N-0424 Oslo, Norway.
  • Nguyen TL; Institute for Cancer Research, Oslo University Hospital, N-0424 Oslo, Norway.
  • Fatkin D; Children's Medical Research Institute, The University of Sydney, Westmead 2145, Australia.
  • Graham RM; Garvan Institute of Medical Research, Sydney 2010, Australia.
  • Giannoulatou E; St Vincent's Clinical School, University of New South Wales, Sydney 2010, Australia.
  • Green MJ; QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
  • Kaplan W; QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
  • Ravishankar S; QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
  • Copty J; Faculty of Medicine. The University of Queensland, Brisbane 4072, Australia.
  • Powell JE; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne 3010, Australia.
  • Cuppen E; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
  • van Eijk K; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton 3800, Australia.
  • Veldink J; Murdoch Children's Research Institute, Royal Children's Hospital, Parkville 3051, Australia.
  • Ahn JH; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne 3010, Australia.
  • Kim JE; St Vincent's Clinical School, University of New South Wales, Sydney 2010, Australia.
  • Randall RL; Molecular Cardiology Division, Victor Chang Cardiac Research Institute, Darlinghurst 2010, Australia.
  • Tucker K; Cardiology Department, St Vincent's Hospital, Sydney 2010, Australia.
  • Judson I; St Vincent's Clinical School, University of New South Wales, Sydney 2010, Australia.
  • Sarin R; Molecular Cardiology Division, Victor Chang Cardiac Research Institute, Darlinghurst 2010, Australia.
  • Ludwig T; St Vincent's Clinical School, University of New South Wales, Sydney 2010, Australia.
  • Genin E; Computational Genomics Division, Victor Chang Cardiac Research Institute, Sydney 2010, Australia.
Science ; 379(6629): 253-260, 2023 01 20.
Article in En | MEDLINE | ID: mdl-36656928
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Sarcoma / Telomere / Germ-Line Mutation / Genetic Predisposition to Disease / Mitosis Limits: Humans Language: En Journal: Science Year: 2023 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Sarcoma / Telomere / Germ-Line Mutation / Genetic Predisposition to Disease / Mitosis Limits: Humans Language: En Journal: Science Year: 2023 Document type: Article