TY - JOUR
T1 - Cancer risk and tumour spectrum in 172 patients with a germline SUFU pathogenic variation: a collaborative study of the SIOPE Host Genome Working Group
AU - Guerrini-Rousseau, Léa
AU - Masliah-Planchon, Julien
AU - Waszak, Sebastian M
AU - Alhopuro, Pia
AU - Benusiglio, Patrick R
AU - Bourdeaut, Franck
AU - Brecht, Ines B
AU - Del Baldo, Giada
AU - Dhanda, Sandeep Kumar
AU - Garrè, Maria Luisa
AU - Gidding, Corrie E M
AU - Hirsch, Steffen
AU - Hoarau, Pauline
AU - Jorgensen, Mette
AU - Kratz, Christian
AU - Lafay-Cousin, Lucie
AU - Mastronuzzi, Angela
AU - Pastorino, Lorenza
AU - Pfister, Stefan M
AU - Schroeder, Christopher
AU - Smith, Miriam Jane
AU - Vahteristo, Pia
AU - Vibert, Roseline
AU - Vilain, Catheline
AU - Waespe, Nicolas
AU - Winship, Ingrid M
AU - Evans, D Gareth
AU - Brugieres, Laurence
N1 - Funding Information:
LB and LG-R have been supported by la Fondation Gustave Roussy campaign: Guérir Le Cancer de l’Enfant au 21ème siècle. DGE and MJS are supported by the National Institute for Health Research (NIHR) BRC Manchester (Grant Reference Number 1215-200074). CPK and SMP have been supported by the Deutsche Kinderkrebsstiftung (DKS2019.13).
Funding Information:
This project was additionally supported by 'la Fondation Gustave Roussy', the Italian Association for Cancer Research (AIRC), the PedBrain Tumor Project contributing to the International Cancer Genome Consortium (ICGC), funded by the German Cancer Aid (109252), the German Federal Ministry of Education and Research (BMBF) (01KU1201A, 01KU1201C) and the BMBF grants BioTop (01EK1502A, 01EK1502B), ICGC-DE-Mining (01KU1505F), MedSys (0315416C) and NGFNplus (01GS0883).
Publisher Copyright:
© 2022 BMJ Publishing Group. All rights reserved.
PY - 2022/6/29
Y1 - 2022/6/29
N2 - Background: Little is known about risks associated with germline SUFU pathogenic 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 Methods: To study tumour risks, we have analysed data of a large cohort of 45 unpublished patients with a germline SUFU PV completed with 127 previously published patients. To reduce the ascertainment bias due to index patient selection, the risk of tumours was evaluated in relatives with SUFU PV (89 patients) using the Nelson-Aalen estimator. Results: Overall, 117/172 (68%) SUFU PV 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 entire SUFU gene and inherited in 73% of cases in which inheritance could be evaluated. Conclusion: Germline SUFU PV 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.
AB - Background: Little is known about risks associated with germline SUFU pathogenic 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 germline SUFU PV completed with 127 previously published patients. To reduce the ascertainment bias due to index patient selection, the risk of tumours was evaluated in relatives with SUFU PV (89 patients) using the Nelson-Aalen estimator. Results: Overall, 117/172 (68%) SUFU PV 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 entire SUFU gene and inherited in 73% of cases in which inheritance could be evaluated. Conclusion: Germline SUFU PV 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.
KW - central nervous system diseases
KW - congenital, hereditary, and neonatal diseases and abnormalities
KW - genetic counseling
KW - genetic predisposition to disease
KW - germ-line mutation
UR - http://europepmc.org/abstract/med/35768194
U2 - 10.1136/jmedgenet-2021-108385
DO - 10.1136/jmedgenet-2021-108385
M3 - Article
C2 - 35768194
SN - 1468-6244
VL - 59
SP - 1123
EP - 1132
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
IS - 11
M1 - 108385
ER -
