{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:32:44Z","timestamp":1792513964541,"version":"4.5.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,9,17]]},"abstract":"\n Background<\/jats:title>\n \n Mutations in the\n \n POT<\/jats:styled-content>\n 1\n <\/jats:italic>\n gene explain abnormally long telomeres and multiple tumors including cardiac angiosarcomas (\n CAS<\/jats:styled-content>\n ). However, the link between long telomeres and tumorigenesis is poorly understood.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Here, we have studied the somatic landscape of 3 different angiosarcoma patients with mutations in the\n \n POT<\/jats:styled-content>\n 1\n <\/jats:italic>\n gene to further investigate this tumorigenesis process. In addition, the genetic landscape of 7\n CAS<\/jats:styled-content>\n patients without mutations in the\n \n POT<\/jats:styled-content>\n 1\n <\/jats:italic>\n gene has been studied. Patients with\n CAS<\/jats:styled-content>\n and nonfunctional\n \n POT<\/jats:styled-content>\n 1\n <\/jats:italic>\n did not repress\n ATR<\/jats:styled-content>\n (ataxia telangiectasia RAD3\u2010related)\u2013dependent\n DNA<\/jats:styled-content>\n damage signaling and showed a constitutive increase of cell cycle arrest and somatic activating mutations in the\n VEGF<\/jats:styled-content>\n (vascular endothelial growth factor)\/angiogenesis pathway (\n \n KDR<\/jats:styled-content>\n <\/jats:italic>\n gene). The same observation was made in\n \n POT<\/jats:styled-content>\n 1\n <\/jats:italic>\n mutation carriers with tumors different from\n CAS<\/jats:styled-content>\n and also in\n CAS<\/jats:styled-content>\n patients without mutations in the\n \n POT<\/jats:styled-content>\n 1\n <\/jats:italic>\n gene but with mutations in other genes involved in\n DNA<\/jats:styled-content>\n damage signaling.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Inhibition of\n POT<\/jats:styled-content>\n 1 function and damage\u2010response malfunction activated\n DNA<\/jats:styled-content>\n damage signaling and increased cell cycle arrest as well as interfered with apoptosis, which would permit acquisition of somatic mutations in the\n VEGF<\/jats:styled-content>\n \/angiogenesis pathway that drives tumor formation. Therapies based on the inhibition of damage signaling in asymptomatic carriers may diminish defects on cell cycle arrest and thus prevent the apoptosis deregulation that leads to the acquisition of driver mutations.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.119.012875","type":"journal-article","created":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T09:02:07Z","timestamp":1568278927000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["POT1 and Damage Response Malfunction Trigger Acquisition of Somatic Activating Mutations in the VEGF Pathway in Cardiac Angiosarcomas"],"prefix":"10.1161","volume":"8","author":[{"given":"Oriol","family":"Calvete","sequence":"first","affiliation":[{"name":"Human Genetics Group Spanish National Cancer Research Center (CNIO) Madrid Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases (CIBERER) Madrid 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