Incomplete penetrance of the predisposition to medulloblastoma associated with germ-line SUFU mutations

• Published in: Journal of medical genetics Vol. 47; no. 2; pp. 142 - 144
• Main Authors: Brugières, Laurence, Pierron, Gaëlle, Chompret, Agnès, Paillerets, Brigitte Bressac-de, Di Rocco, Federico, Varlet, Pascale, Pierre-Kahn, Alain, Caron, Olivier, Grill, Jacques, Delattre, Olivier
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.02.2010; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Adult; Biological and medical sciences; Breast cancer; Cancer: CNS; Cerebellar Neoplasms - genetics; Child, Preschool; childhood; desmoplastic medulloblastoma; DNA Mutational Analysis; familial medulloblastoma; Families & family life; Family; Female; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genetic Predisposition to Disease; genetics; Genetics of eukaryotes. Biological and molecular evolution; Germ-Line Mutation; Humans; Infant; Male; Medical genetics; Medical sciences; medulloblastoma; Medulloblastoma - genetics; Molecular and cellular biology; Mutation; neuro oncology; Neurology; paediatric oncology; Pedigree; Penetrance; Remission (Medicine); Repressor Proteins - genetics; SUFU; Tumors of the nervous system. Phacomatoses; Human; Nervous system diseases; Pathogenesis; Malignant tumor; Genetic determinism; Cerebral disorder; Germ line; Medulloblastoma; Gene penetrance; Central nervous system disease; Predisposition; Genetics; Mutation; Cancer
• ISSN: 0022-2593; 1468-6244
• DOI: 10.1136/jmg.2009.067751

Methods and resultsGermline SUFU mutations were identified in two families with several children under 3 years of age diagnosed with medulloblastoma. All medulloblastomas in which the histology was reviewed were of the desmoplastic subtype, including three with the rare extensive nodularity subtype. In both families, the mutation detected in the SUFU gene was a frameshift mutation. Among the 25 mutation carriers identified in the two families, seven developed medulloblastomas.ConclusionsThis report highlights three features of SUFU related tumours. These are mainly medulloblastomas with extensive nodularity or typical desmoplastic/nodular medulloblastomas. These tumours mostly, if not exclusively, appear during the first 3 years of life. The penetrance of the mutation is incomplete.