Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma
Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma
复制标题
DOI：
10.1038/ng.861
复制
发表时间：
2011-07-01
期刊：
影响因子：
30.8
通讯作者：
Cascon, Alberto
中科院分区：
文献类型：
--
作者：
Comino-Mendez, Inaki;Gracia-Aznarez, Francisco J.;Cascon, Alberto
遗传性嗜铬细胞瘤（PCC）通常是由迄今为止描述的9种易感基因之一的种系突变引起的（1 - 4），但也有家族性病例在这些已知基因中没有突变。我们对三个遗传性PCC（病例）的无关个体的外显子组进行了测序，并确定了MAX（MYC相关因子X基因）的突变。肿瘤中MAX蛋白的缺失和由单亲二体性引起的杂合性丢失支持MAX改变参与疾病。一项对59例PCC病例的随访研究发现了5个额外的MAX突变，并表明MAX突变与恶性结局和优先父系传播有关。MYC-MAX-MXD1网络参与神经嵴细胞肿瘤的发生和进展进一步得到大鼠PCC（PC12）细胞中功能性MAX的缺乏（5）和神经母细胞瘤中MYCN的扩增（6）的支持，并表明MAX功能的丧失与转移潜力相关。
Hereditary pheochromocytoma (PCC) is often caused by germline mutations in one of nine susceptibility genes described to date(1-4), but there are familial cases without mutations in these known genes. We sequenced the exomes of three unrelated individuals with hereditary PCC (cases) and identified mutations in MAX, the MYC associated factor X gene. Absence of MAX protein in the tumors and loss of heterozygosity caused by uniparental disomy supported the involvement of MAX alterations in the disease. A follow-up study of a selected series of 59 cases with PCC identified five additional MAX mutations and suggested an association with malignant outcome and preferential paternal transmission of MAX mutations. The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is further supported by the lack of functional MAX in rat PCC (PC12) cells(5) and by the amplification of MYCN in neuroblastoma(6) and suggests that loss of MAX function is correlated with metastatic potential.