Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes
Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes
复制标题
DOI：
10.1038/bjc.2015.75
复制
发表时间：
2015-04-14
影响因子：
8.8
通讯作者：
Zenker, M.
中科院分区：
文献类型：
--
作者：
Kratz, C. P.;Franke, L.;Zenker, M.
背景资料：影响Ras-MAPK通路组分的体细胞突变是癌症的常见特征，而生殖系Ras通路突变导致发育障碍，包括努南、科斯特洛和心-面-皮肤综合征。这些'RASopathies'也代表癌症倾向的综合征，但定量的癌症风险仍然unknowed.Methods：我们调查了儿童癌症的发生率，包括中枢神经系统的良性和恶性肿瘤，在一组735个人与生殖细胞突变的Ras信号通路基因，通过匹配他们的信息与德国儿童癌症登记。我们在整个RASopathy队列中观察到12例癌症病例，而预期为1.12例（基于德国人群的发病率）。这相当于所有儿童癌症合并的风险增加10.5倍（标准化发病率比（SIR）= 10.5，95%置信区间= 5.4-18.3）。具体癌症包括青少年粒单核细胞白血病= 4;脑瘤= 3;急性淋巴细胞白血病= 2;横纹肌肉瘤= 2;神经母细胞瘤= 1。努南综合征患儿的儿童期癌症SIR为8.1，而Costello综合征患儿的儿童期癌症SIR为42.4。结论：本研究首次提供了Ras信号通路基因的生殖系突变与儿童期白血病和实体瘤风险增加相关的定量证据。
Background: Somatic mutations affecting components of the Ras-MAPK pathway are a common feature of cancer, whereas germline Ras pathway mutations cause developmental disorders including Noonan, Costello, and cardio-facio-cutaneous syndromes. These 'RASopathies' also represent cancer-prone syndromes, but the quantitative cancer risks remain unknown.Methods: We investigated the occurrence of childhood cancer including benign and malignant tumours of the central nervous system in a group of 735 individuals with germline mutations in Ras signalling pathway genes by matching their information with the German Childhood Cancer Registry.Results: We observed 12 cases of cancer in the entire RASopathy cohort vs 1.12 expected (based on German population-based incidence rates). This corresponds to a 10.5-fold increased risk of all childhood cancers combined (standardised incidence ratio (SIR) = 10.5, 95% confidence interval = 5.4-18.3). The specific cancers included juvenile myelomonocytic leukaemia = 4; brain tumour = 3; acute lymphoblastic leukaemia = 2; rhabdomyosarcoma = 2; and neuroblastoma = 1. The childhood cancer SIR in Noonan syndrome patients was 8.1, whereas that for Costello syndrome patients was 42.4.Conclusions: These data comprise the first quantitative evidence documenting that the germline mutations in Ras signalling pathway genes are associated with increased risks of both childhood leukaemia and solid tumours.