Heritable defects in telomere and mitotic function selectively predispose to sarcomas - Archive ouverte HAL
Article Dans Une Revue Science Année : 2023

Heritable defects in telomere and mitotic function selectively predispose to sarcomas

Mandy Ballinger
Swetansu Pattnaik
Piyushkumar Mundra
Milita Zaheed
Emma Rath
Peter Priestley
Jonathan Baber
Isabelle Ray-Coquard
Nicholas Isambert
  • Fonction : Auteur
Sylvain Causeret
Winette van der Graaf
Ajay Puri
Beatrice Seddon
  • Fonction : Auteur
Coonoor Chandrasekar
  • Fonction : Auteur
Joshua Schiffman
Andrew Brohl
Ola Myklebost
Leonardo Meza-Zepeda
Maya Kansara
Nicola Waddell
Olga Kondrashova
John Pearson
Andrew Barbour
  • Fonction : Auteur
Shuai Li
Tuong Nguyen
Diane Fatkin
Robert Graham
Eleni Giannoulatou
Melissa Green
Warren Kaplan
Shyamsundar Ravishankar
Joseph Copty
Joseph Powell
Edwin Cuppen
Kristel van Eijk
  • Fonction : Auteur
Jan Veldink
Jin-Hee Ahn
Jeong Eun Kim
R. Lor Randall
Kathy Tucker
Ian Judson
Rajiv Sarin
Jean-Francois Deleuze
Michelle Haber
Glenn Marshall
Murray Cairns
Jean-Yves Blay
David Thomas

Résumé

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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Dates et versions

hal-04188088 , version 1 (25-08-2023)

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Citer

Mandy Ballinger, Swetansu Pattnaik, Piyushkumar Mundra, Milita Zaheed, Emma Rath, et al.. Heritable defects in telomere and mitotic function selectively predispose to sarcomas. Science, 2023, 379 (6629), pp.253-260. ⟨10.1126/science.abj4784⟩. ⟨hal-04188088⟩
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