Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Nat Genet. 2011 Jun 19;43(7):663-7. doi: 10.1038/ng.861.
Hereditary pheochromocytoma (PCC) is often caused by germline mutations in one of nine susceptibility genes described to date, 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 and by the amplification of MYCN in neuroblastoma and suggests that loss of MAX function is correlated with metastatic potential.
遗传性嗜铬细胞瘤（PCC）通常由迄今为止描述的九个易感性基因中的一个种系突变引起，但也有家族性病例没有这些已知基因的突变。我们对三个无关联的遗传性 PCC（病例）个体进行了外显子组测序，发现了 MAX（MYC 相关因子 X 基因）的突变。肿瘤中缺乏 MAX 蛋白和单亲二倍体引起的杂合性丢失支持 MAX 改变参与了疾病。对 PCC 的一个选定系列 59 例的后续研究发现了另外五个 MAX 突变，并提示与恶性结局和 MAX 突变的优先父系传递有关。MYC-MAX-MXD1 网络在神经嵴细胞肿瘤的发生和进展中的参与还得到了缺乏功能性 MAX 的大鼠 PCC（PC12）细胞以及神经母细胞瘤中 MYCN 扩增的支持，这表明 MAX 功能丧失与转移潜能相关。
