Institut Gustave Roussy, Villejuif, France.
J Clin Oncol. 2012 Jun 10;30(17):2087-93. doi: 10.1200/JCO.2011.38.7258. Epub 2012 Apr 16.
Germline mutations of the SUFU gene have been shown to be associated with genetic predisposition to medulloblastoma, mainly in families with multiple cases of medulloblastoma and/or in patients with symptoms similar to those of Gorlin syndrome. To evaluate the contribution of these mutations to the genesis of sporadic medulloblastomas, we screened a series of unselected patients with medulloblastoma for germline SUFU mutations.
A complete mutational analysis of the SUFU gene was performed on genomic DNA in all 131 consecutive patients treated for medulloblastoma in the pediatrics department of the Institut Gustave Roussy between 1972 and 2009 and for whom a blood sample was available.
We identified eight germline mutations of the SUFU gene: one large genomic duplication and seven point mutations. Mutations were identified in three of three individuals with medulloblastoma with extensive nodularity, four of 20 with desmoplastic/nodular medulloblastomas, and one of 108 with other subtypes. All eight patients were younger than 3 years of age at diagnosis. The mutations were inherited from the healthy father in four of six patient cases in which the parents accepted genetic testing; de novo mutations accounted for the other two patient cases. Associated events were macrocrania in six patients, hypertelorism in three patients, and multiple basal cell carcinomas in the radiation field after age 18 years in one patient.
These data indicate that germline SUFU mutations were responsible for a high proportion of desmoplastic medulloblastoma in children younger than 3 years of age. Genetic testing should be offered to all children diagnosed with sonic hedgehog-driven medulloblastoma at a young age.
已证实 SUFU 基因的种系突变与遗传易感性髓母细胞瘤有关，主要是在多发性髓母细胞瘤家族或具有类似 Gorlin 综合征症状的患者中。为了评估这些突变对散发性髓母细胞瘤发生的贡献，我们对 1972 年至 2009 年期间在 Institut Gustave Roussy 儿科部门治疗的连续 131 例未经选择的髓母细胞瘤患者的基因组 DNA 进行了 SUFU 基因突变的全面分析，并且这些患者都有可用的血样。
对 1972 年至 2009 年期间在 Institut Gustave Roussy 儿科部门治疗的连续 131 例未经选择的髓母细胞瘤患者的基因组 DNA 进行了 SUFU 基因突变的全面分析，并且这些患者都有可用的血样。
我们鉴定出了 SUFU 基因的八个种系突变：一个大的基因组重复和七个点突变。在三个广泛结节性髓母细胞瘤患者中发现了三个突变，在 20 个促结缔组织增生性/结节性髓母细胞瘤患者中有四个突变，在 108 个其他亚型患者中有一个突变。所有 8 例患者的诊断年龄均小于 3 岁。在接受遗传检测的 6 例患者中，4 例的突变是从健康父亲遗传而来；另外 2 例患者的突变是新生突变。在 6 例患者中存在巨颅，在 3 例患者中存在眼距过宽，在 1 例患者中在 18 岁后在放疗野中出现多发性基底细胞癌。
这些数据表明，种系 SUFU 突变导致了很大一部分 3 岁以下儿童的促结缔组织增生性髓母细胞瘤。应向所有年轻的 Sonic Hedgehog 驱动型髓母细胞瘤患者提供遗传检测。
