Leukemia in cardio-facio-cutaneous (CFC) syndrome:: A patient with a germline mutation in BRAF proto-oncogene
Leukemia in cardio-facio-cutaneous (CFC) syndrome:: A patient with a germline mutation in BRAF proto-oncogene
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DOI：
10.1097/mph.0b013e3180547136
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发表时间：
2007-05-01
影响因子：
1.2
通讯作者：
Aoki, Yoko
中科院分区：
文献类型：
--
作者：
Makita, Yoshio;Narumi, Yoko;Aoki, Yoko
心-面-皮（CFC）综合征是一种多发性先天性异常/智力低下综合征，其特征是独特的面部外观、外胚层异常和心脏缺陷。临床上，它与Noonan综合征和Costello综合征重叠，这两种综合征是由编码RAS/MAPK（丝裂原活化蛋白激酶）途径分子的2个基因（分别为PTPN11和HRAS）突变引起的。最近，在CFC综合征患者中发现了KRAS、BRAF和MEK1/2的突变。KRAS和BRAF的体细胞突变已在多种肿瘤中发现。相比之下，在CFC综合征中未发现与恶性肿瘤的关联。我们在此报告一名九岁男童，诊断为CFC症候群及急性淋巴细胞白血病。对KRAS和BRAF全编码区进行测序分析，发现BRAF E501G （1502A -> G）突变为新生种系突变。对于患有CFC综合征的儿童，应考虑分子诊断和仔细观察，因为他们的原癌基因有种系突变，并可能发展为恶性肿瘤。
Cardio-facio-cutancous (CFC) syndrome is a multiple congenital anomaly/mental retardation syndrome characterized by a distinctive facial appearance, ectodermal abnormalities, and heart defects. Clinically, it overlaps with both Noonan syndrome and Costello syndrome, which are caused by mutations in 2 genes that encode molecules of the RAS/MAPK (mitogen activated protein kinase) pathway (PTPN11 and HRAS, respectively). Recently, mutations in KRAS, BRAF, and MEK1/2 have been identified in patients with CFC syndrome. Somatic mutations in KRAS and BRAF have been identified in various tumors. In contrast, the association with malignancy has not been noticed in CFC syndrome. Here we report a 9-year-old boy diagnosed with CFC syndrome and acute lymphoblastic leukemia. Sequencing analysis of the entire coding region of KRAS and BRAF showed a de novo germline BRAF E501G (1502A -> G) mutation. Molecular diagnosis and careful observations should be considered in children with CFC syndrome because they have germline mutations in proto-oncogenes and might develop malignancy.