BACKGROUND: Germline mutations of the SUFU gene have recently been described in association to medulloblastoma. Only a few cases have been described in literature so far. PATIENTS AND METHODS: We performed a retrospective review of the clinical and molecular data of all patients in whom a germline SUFU mutation had been diagnosed in Gustave Roussy and Institut Curie genetics laboratories. RESULTS: 21 probands had a germline SUFU mutation. Nineteen patients were diagnosed with a medulloblastoma at a median age of 18 months [range 1-35] (desmoplastic = 9, extensive nodularity = 6, classical = 4). Two others patients were tested because of a familial history of medulloblastoma and criteria for a Gorlin syndrom without germline PTCH mutation. Macrocrania was frequently documented. Medulloblastoma in siblings or early death from brain tumor were described in several families. Mutations were inherited in 12/13 patients whose parents underwent genetic testing and de novo in 2 cases. Thirty-six healthy carriers have been identified. Second malignancies were described in 3 medulloblastoma patients including basocellular carcinomas (CBC) (1pt), ovarian tumor and meningioma (1pt) and thyroid carcinoma (1pt). Several others cancers including early breast cancer and sarcomas were diagnosed in mutation carriers. CONCLUSION: SUFU germline mutations predispose to medulloblastomas mostly of desmoplastic/nodular or extensive nodularity subtypes during the first 3 years of life, often associated with macrocrania. The incidence of CBC seems lower than in classic Gorlin syndrome. Due to incomplete penetrance, genetic counselling is difficult. International collaboration is necessary in order to better define the risk associated with these mutations and guidelines for surveillance.

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