Département de Cancérologie de l'Enfant et de l'Adolescent, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
Service de neuropathologie, Hôpital Sainte-Anne, Université Paris Descartes, Paris, France.
Neuro Oncol. 2018 Jul 5;20(8):1122-1132. doi: 10.1093/neuonc/nox228.
Germline mutations of suppressor of fused homolog (SUFU) predispose to sonic hedgehog (SHH) medulloblastoma. Germline SUFU mutations have been reported in nevoid basal cell carcinoma syndrome (NBCCS), but little is known about the cancer risk and clinical spectrum.
We performed a retrospective review of all patients with medulloblastoma and a germline SUFU mutation in France.
Twenty-two patients from 17 families were identified with medulloblastoma and a germline SUFU mutation (median age at diagnosis: 16.5 mo). Macrocrania was present in 20 patients, but only 5 met the diagnostic criteria for NBCCS. Despite treatment with surgery and chemotherapy, to avoid radiotherapy in all patients except one, the outcome was worse than expected for SHH medulloblastoma, due to the high incidence of local relapses (8/22 patients) and second malignancies (n = 6 in 4/22 patients). The 5-year progression-free survival and overall survival rates were 42% and 66%. Mutations were inherited in 79% of patients, and 34 additional SUFU mutation carriers were identified within 14 families. Medulloblastoma penetrance was incomplete, but higher than in Patched 1 (PTCH1) mutation carriers. Besides medulloblastoma, 19 other tumors were recorded among the 56 SUFU mutation carriers, including basal cell carcinoma (BCC) in 2 patients and meningioma in 3 patients.
Germline SUFU mutations strongly predispose to medulloblastoma in the first years of life, with worse prognosis than usually observed for SHH medulloblastoma. The clinical spectrum differs between SUFU and PTCH1 mutation carriers, and BCC incidence is much lower in SUFU mutation carriers. The optimal treatment of SUFU mutation-associated medulloblastoma has not been defined.
融合抑制因子（SUFU）胚系突变可导致 Sonic Hedgehog（SHH）型髓母细胞瘤。神经嵴发育不全基底细胞瘤综合征（NBCCS）患者存在 SUFU 胚系突变，但此类突变患者的癌症风险和临床表现知之甚少。
我们对法国所有患有髓母细胞瘤和 SUFU 胚系突变的患者进行了回顾性研究。
共发现 17 个家系的 22 例患者存在髓母细胞瘤和 SUFU 胚系突变（诊断时的中位年龄为 16.5 个月）。20 例患者存在巨颅症，但仅有 5 例符合 NBCCS 的诊断标准。尽管所有患者（除 1 例外）均接受了手术和化疗治疗，以避免放疗，但由于局部复发率高（22 例患者中有 8 例）和第二恶性肿瘤发生率高（4 个家系中有 6 例患者发生了 6 例第二恶性肿瘤），其预后较 SHH 型髓母细胞瘤差。5 年无进展生存率和总生存率分别为 42%和 66%。突变以 79%的患者遗传，在 14 个家系中还发现了 34 例额外的 SUFU 突变携带者。髓母细胞瘤的外显率不完全，但高于 Patched 1（PTCH1）突变携带者。在 56 例 SUFU 突变携带者中，除髓母细胞瘤外，还记录了 19 种其他肿瘤，包括 2 例患者的基底细胞癌（BCC）和 3 例患者的脑膜瘤。
SUFU 胚系突变可强烈导致儿童早期发生髓母细胞瘤，其预后较 SHH 型髓母细胞瘤差。SUFU 突变携带者与 PTCH1 突变携带者的临床表现不同，且 SUFU 突变携带者的 BCC 发生率明显较低。SUFU 突变相关髓母细胞瘤的最佳治疗方法尚未确定。
