{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:24:33Z","timestamp":1790871873281,"version":"4.1.0"},"reference-count":31,"publisher":"BMJ","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2010,11,24]]},"published-print":{"date-parts":[[2011,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Constitutional\n                      <jats:italic>DICER1<\/jats:italic>\n                      mutations were recently reported to cause familial pleuropulmonary blastoma (PPB).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      To investigate the contribution and phenotypic spectrum of constitutional and somatic\n                      <jats:italic>DICER1<\/jats:italic>\n                      mutations to cancer.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      The authors sequenced\n                      <jats:italic>DICER1<\/jats:italic>\n                      in constitutional DNA from 823 unrelated patients with a variety of tumours and in 781 cancer cell lines. Constitutional\n                      <jats:italic>DICER1<\/jats:italic>\n                      mutations were identified in 19 families including 11\/14 with PPB, 2\/3 with cystic nephroma, 4\/7 with ovarian Sertoli\u2013Leydig-type tumours, 1\/243 with Wilms tumour (this patient also had a Sertoli\u2013Leydig tumour), 1\/1 with intraocular medulloepithelioma (this patient also had PPB), 1\/86 with medulloblastoma\/infratentorial primitive neuroectodermal tumour, and 1\/172 with germ cell tumour. The inheritance was investigated in 17 families.\n                      <jats:italic>DICER1<\/jats:italic>\n                      mutations were identified in 25 relatives: 17 were unaffected, one mother had ovarian Sertoli\u2013Leydig tumour, one half-sibling had cystic nephroma, and six relatives had non-toxic thyroid cysts\/goitre. Analysis of eight tumours from\n                      <jats:italic>DICER1<\/jats:italic>\n                      mutation-positive patients showed universal retention of the wild-type allele.\n                      <jats:italic>DICER1<\/jats:italic>\n                      truncating mutations were identified in 4\/781 cancer cell lines; all were in microsatellite unstable lines and therefore unlikely to be driver mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Constitutional DICER1 haploinsufficiency predisposes to a broad range of tumours, making a substantial contribution to PPB, cystic nephroma and ovarian Sertoli\u2013Leydig tumours, but a smaller contribution to other tumours. Most mutation carriers are unaffected, indicating that tumour risk is modest. The authors define the clinical contexts in which\n                      <jats:italic>DICER1<\/jats:italic>\n                      mutation testing should be considered, the associated tumour risks, and the implications for at-risk individuals. They have termed this condition \u2018\n                      <jats:italic>DICER1<\/jats:italic>\n                      syndrome\u2019.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Accession numbers<\/jats:title>\n                    <jats:p>\n                      The cDNA Genbank accession number for the\n                      <jats:italic>DICER1<\/jats:italic>\n                      sequence reported in this paper is NM_030621.2.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmg.2010.083790","type":"journal-article","created":{"date-parts":[[2011,1,25]],"date-time":"2011-01-25T20:35:35Z","timestamp":1295987735000},"page":"273-278","source":"Crossref","is-referenced-by-count":331,"title":["<i>DICER1<\/i>\n                    syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition 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