DICER1 syndrome – clarifying the diagnosis, clinical features and management implications of a pleiotropic tumor predisposition syndrome

Dicer1 is essential in the production of microRNAs and germline DICER1 mutations have been reported to cause familial pleuropulmonary blastoma (PPB), a rare childhood lung tumor.  Our work defines the phenotype associated with this gene; sporadic and familial PPB, cystic nephroma, ovarian Sertoli-Leydig tumor and cystic thyroid disease.  There was no loss of the wildtype allele (second hit) in any tumor therefore DICER1 does not act as a classical tumor suppressor gene. Most mutation carriers within families are unaffected indicating the risk of tumors is modest.  Analyses in cancer cell-lines suggest that somatic DICER1 mutations do not make a substantial contribution to cancer.  We define the clinical contexts in which DICER1 mutation testing should be considered and the implications for at-risk individuals.  We have termed this condition ‘DICER1 syndrome’. (By Dr. Ingrid Slade, http://jmg.bmj.com/content/early/2011/01/24/jmg.2010.083790?papetoc)