RARE-21. CANCER SPECTRUM IN GERMLINE SUFU MUTATION CARRIERS: A COLLABORATIVE PROJECT OF THE SIOPE HOST GENOME WORKING GROUP

BACKGROUND: Little is known about cancer risk associated with pathogenic germline SUFU variants. METHODS: Data of all previously published and 25 still unpublished patients with a pathogenic germline SUFU mutation were compiled. RESULTS: 124 patients in 67 families were identified, most of them ascertained after the occurrence of a medulloblastoma (MB) or as part of Gorlin syndrome cohorts. Overall, 30 patients were healthy carriers and 94 patients developed a total of 129 tumors (up to 4 tumors/patient): 68 MBs, always as first tumor (median age at diagnosis: 1.5yr [0.1–5]), 22 patients with at least 1 basal cell carcinoma (BCC) (median 10/patient) (median age at first BCC: 43yr, [17–52]), 15 meningiomas (median age 43yr, [13–72]), 7 ovarian stromal/fibrous tumors (median age 12yr [5–34]), and 17 other tumors including 5 sarcomas (median age: 50yr [7–79]). Median age at last follow-up was 30yr. Nineteen patients died, including 11 from MB. Second malignancies were diagnosed in 21 patients including 13 in MB survivors. Mutations were inherited in 58/66 (88%) of cases in which inheritance could be tested and de novo in 8. In 6/67 families (9%), >2 children were diagnosed with a MB. CONCLUSION: In this large cohort of germline SUFU mutation carriers, MB in infants is the most frequent tumor but the spectrum also includes typical Gorlin syndrome tumors (BCC, meningiomas, and ovarian stromal/fibrous tumors) either as first tumors or as second malignancies. This broad tumor spectrum and the high risk of second malignancies justify the implementation of specific cancer surveillance programs.