Heritable defects in telomere and mitotic function selectively predispose to sarcomas.

Fiche publication

Date publication

janvier 2023

Journal

Science (New York, N.Y.)

Auteurs

Membres identifiés du Cancéropôle Est :
Pr KURTZ Jean-Emmanuel

Tous les auteurs :
Ballinger ML, Pattnaik S, Mundra PA, Zaheed M, Rath E, Priestley P, Baber J, Ray-Coquard I, Isambert N, Causeret S, van der Graaf WTA, Puri A, Duffaud F, Le Cesne A, Seddon B, Chandrasekar C, Schiffman JD, Brohl AS, James PA, Kurtz JE, Penel N, Myklebost O, Meza-Zepeda LA, Pickett H, Kansara M, Waddell N, Kondrashova O, Pearson JV, Barbour AP, Li S, Nguyen TL, Fatkin D, Graham RM, Giannoulatou E, Green MJ, Kaplan W, Ravishankar S, Copty J, Powell JE, Cuppen E, van Eijk K, Veldink J, Ahn JH, Kim JE, Randall RL, Tucker K, Judson I, Sarin R, Ludwig T, Genin E, Deleuze JF, ,Haber M, Marshall G, Cairns MJ, Blay JY, ,Thomas DM, Tattersall M, Neuhaus S, Lewis C, Tucker K, Carey-Smith R, Wood D, Porceddu S, Dickinson I, Thorne H, James P, Ray-Coquard I, Blay JY, Cassier P, Le Cesne A, Duffaud F, Penel N, Isambert N, Kurtz JE, Puri A, Sarin R, Ahn JH, Kim JE, Ward I, Judson I, van der Graaf W, Seddon B, Chandrasekar C, Rickar R, Hennig I, Schiffman J, Randall RL, Silvestri A, Zaratzian A, Tayao M, Walwyn K, Niedermayr E, Mang D, Clark R, Thorpe T, MacDonald J, Riddell K, Mar J, Fennelly V, Wicht A, Zielony B, Galligan E, Glavich G, Stoeckert J, Williams L, Djandjgava L, Buettner I, Osinki C, Stephens S, Rogasik M, Bouclier L, Girodet M, Charreton A, Fayet Y, Crasto S, Sandupatla B, Yoon Y, Je N, Thompson L, Fowler T, Johnson B, Petrikova G, Hambridge T, Hutchins A, Bottero D, Scanlon D, Stokes-Denson J, Génin E, Campion D, Dartigues JF, Deleuze JF, Lambert JC, Redon R, Ludwig T, Grenier-Boley B, Letort S, Lindenbaum P, Meyer V, Quenez O, Dina C, Bellenguez C, Le Clézio CC, Giemza J, Chatel S, Férec C, Le Marec H, Letenneur L, Nicolas G, Rouault K

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/36656928

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.