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Cancer risk and tumour spectrum in 172 patients with a germline SUFU pathogenic variation: a collaborative study of the SIOPE Host Genome Working Group

Published inJournal of medical genetics, vol. 59, no. 11, p. 1123-1132
Publication date2022-06-29
First online date2022-06-29
Abstract

Background: Little is known about risks associated with germlineSUFUpathogenic variants (PVs) known as a cancer predisposition syndrome.

Methods: To study tumour risks, we have analysed data of a large cohort of 45 unpublished patients with a germlineSUFUPV completed with 127 previously published patients. To reduce the ascertainment bias due to index patient selection, the risk of tumours was evaluated in relatives withSUFUPV (89 patients) using the Nelson-Aalen estimator.

Results: Overall, 117/172 (68%)SUFUPV carriers developed at least one tumour: medulloblastoma (MB) (86 patients), basal cell carcinoma (BCC) (25 patients), meningioma (20 patients) and gonadal tumours (11 patients). Thirty-three of them (28%) had multiple tumours. Median age at diagnosis of MB, gonadal tumour, first BCC and first meningioma were 1.5, 14, 40 and 44 years, respectively. Follow-up data were available for 160 patients (137 remained alive and 23 died). The cumulative incidence of tumours in relatives was 14.4% (95% CI 6.8 to 21.4), 18.2% (95% CI 9.7 to 25.9) and 44.1% (95% CI 29.7 to 55.5) at the age of 5, 20 and 50 years, respectively. The cumulative risk of an MB, gonadal tumour, BCC and meningioma at age 50 years was: 13.3% (95% CI 6 to 20.1), 4.6% (95% CI 0 to 9.7), 28.5% (95% CI 13.4 to 40.9) and 5.2% (95% CI 0 to 12), respectively. Sixty-four different PVs were reported across the entireSUFUgene and inherited in 73% of cases in which inheritance could be evaluated.

Conclusion: GermlineSUFUPV carriers have a life-long increased risk of tumours with a spectrum dominated by MB before the age of 5, gonadal tumours during adolescence and BCC and meningioma in adulthood, justifying fine-tuned surveillance programmes.

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Keywords
  • Central nervous system diseases
  • Congenital, hereditary, and neonatal diseases and abnormalities
  • Genetic counseling
  • Genetic predisposition to disease
  • Germ-line mutation
Citation (ISO format)
GUERRINI-ROUSSEAU, Léa et al. Cancer risk and tumour spectrum in 172 patients with a germline SUFU pathogenic variation: a collaborative study of the SIOPE Host Genome Working Group. In: Journal of medical genetics, 2022, vol. 59, n° 11, p. 1123–1132. doi: 10.1136/jmedgenet-2021-108385
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ISSN of the journal0022-2593
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