Abstract：
In 2002, heterozygous suppressor of fused variants (SUFU+/-) in the germline were described to have a tumor suppressor role in the development of pediatric medulloblastoma (MB). Other neoplasms associated with pathologic germline SUFU+/- variants have also been described among patients with basal cell nevus syndrome (BCNS; BCNS is also known as Gorlin syndrome, nevoid basal cell carcinoma [BCC] syndrome or Gorlin-Goltz syndrome; OMIM 109400), an autosomal-dominant cancer predisposition syndrome. The phenotype of patients with germline SUFU+/- variants is very poorly characterized due to a paucity of large studies with long-term follow-up. As such, there is a clinical need to better characterize the spectrum of neoplasms among patients with germline SUFU+/- variants so that clinicians can provide accurate counseling and optimize tumor surveillance strategies. The objective of this study is to perform a scoping review to map the evidence on the rate of medulloblastoma and to describe the spectrum of other neoplasms among patients with germline SUFU+/- variants. A review of all published literature in PubMed (MEDLINE), EMBASE, Cochrane, and Web of Science were searched from the beginning of each respective database until October 9, 2021. Studies of pediatric and adult patients with a confirmed germline SUFU+/- variant who were evaluated for the presence of any neoplasm (benign or malignant) were included. There were 176 patients (N = 30 studies) identified with a confirmed germline SUFU+/- variant who met inclusion criteria. Data were extracted from two cohort studies, two case-control studies, 18 case series, and eight case reports. The median age at diagnosis of a germline SUFU+/- variant was 4.5 years where 44.4% identified as female and 13.4% of variants were de novo. There were 34 different neoplasms (benign and malignant) documented among patients with confirmed germline SUFU+/- variants, and the most common were medulloblastoma (N = 59 patients), BCC (N = 21 patients), and meningioma (N = 19 patients). The median age at medulloblastoma diagnosis was 1.42 years (range 0.083-3; interquartile range 1.2). When data were available for these three most frequent neoplasms (N = 95 patients), 31 patients (32.6%) had neither MB, BCC nor meningioma; 51 patients (53.7%) had one of medulloblastoma or BCC or meningioma; eight patients (8.4%) had two of medulloblastoma or BCC or meningioma, and five patients (5.3%) had medulloblastoma and BCC and meningioma. This is the first study to synthesize the data on the frequency and spectrum of neoplasms specifically among patients with a confirmed germline SUFU+/- variant. This scoping review is a necessary step forward in optimizing evidence-based tumor surveillance strategies for medulloblastoma and estimating the risk of other neoplasms that could impact patient outcomes.
摘要：
2002年，种系中融合变体（SUFU/-）的杂合抑制因子被描述为在小儿髓母细胞瘤（MB）的发展中具有肿瘤抑制作用。在基底细胞痣综合征患者中也描述了与病理性种系SUFU+/-变异相关的其他肿瘤（BCNS;BCNS也称为Gorlin综合征，中性基底细胞癌[BCC]综合征或Gorlin-Goltz综合征；OMIM109400），常染色体显性遗传的癌症易感性综合征。由于缺乏长期随访的大型研究，具有种系SUFU+/-变体的患者的表型特征非常差。因此，临床上需要更好地表征具有种系SUFU+/-变异体的患者中的肿瘤谱,以便临床医生能够提供准确的咨询并优化肿瘤监测策略.这项研究的目的是进行范围审查，以绘制髓母细胞瘤发生率的证据，并描述具有种系SUFU/-变异的患者中其他肿瘤的频谱。对PubMed（MEDLINE）中所有已发表文献的评论，EMBASE,科克伦,和WebofScience从每个数据库的开头开始搜索，直到2021年10月9日。包括对已确认种系SUFU/-变体的儿科和成人患者的研究，这些患者被评估是否存在任何肿瘤（良性或恶性）。有176名患者(N=30项研究)鉴定为符合纳入标准的确认种系SUFU+/-变体。数据来自两项队列研究，两项病例对照研究，18个案例系列，8例病例报告诊断种系SUFU+/-变体的中位年龄为4.5岁,其中44.4%被鉴定为女性,13.4%的变体为从头。有34个不同的肿瘤（良性和恶性）的患者证实种系SUFU+/-变异，最常见的是髓母细胞瘤（N=59例），BCC（N=21例），和脑膜瘤（N=19例）。诊断为髓母细胞瘤的中位年龄为1.42岁（范围为0.083-3；四分位间距为1.2）。当这三种最常见的肿瘤（N=95例）的数据可用时，31例患者(32.6%)没有MB，BCC或脑膜瘤；51例（53.7％）有髓母细胞瘤或BCC或脑膜瘤之一；8例（8.4％）有髓母细胞瘤或BCC或脑膜瘤，5例患者（5.3％）有髓母细胞瘤，BCC和脑膜瘤。这是第一项综合肿瘤频率和频谱数据的研究，特别是在确认了种系SUFU/-变体的患者中。这项范围审查是优化髓母细胞瘤循证肿瘤监测策略和估计可能影响患者预后的其他肿瘤风险的必要步骤。
