Germline and germline mosaic PTEN mutations associated with a Proteus-like syndrome of hemihypertrophy, lower limb asymmetry, arteriovenous malformations and lipomatosis
Germline and germline mosaic PTEN mutations associated with a Proteus-like syndrome of hemihypertrophy, lower limb asymmetry, arteriovenous malformations and lipomatosis
复制标题
DOI：
10.1093/hmg/9.5.765
复制
发表时间：
2000-03-22
影响因子：
3.5
通讯作者：
Eng, C
中科院分区：
文献类型：
--
作者：
Zhou, XP;Marsh, DJ;Eng, C
胚系PTEN突变导致Cowden综合征(CS)和Bannayan-Riley-RuvalCaba综合征(BRR)这两种错构瘤-肿瘤综合征，体细胞PTEN突变或多或少地参与了各种散发性肿瘤的发生。PTEN是一种肿瘤抑制因子和双特异性磷酸酶，它通过磷酸肌醇-3-激酶和AKT途径中的脂磷酸酶活性影响细胞凋亡，并通过粘着斑激酶途径抑制细胞扩散。CS和ERR具有一些共同的特征，如错构瘤和脂肪瘤病，为了确定其他以过度生长和脂肪瘤为特征的综合征是否属于PTEN综合征谱的一部分，我们确定了6名患有过度生长和脂肪瘤但不符合CS或ERR诊断标准的个体。5人患有变形杆菌综合征，1人患有变形杆菌样综合征。当对生殖系DNA和每个病例至少一个受累组织的DNA进行PTEN突变检测时，只有变形杆菌样患者被发现携带生殖系R335X突变。有趣的是，从生理上不同的部位采集的脂肪瘤样肿块、表皮样痣和动静脉畸形组织都被发现在与种系R335X相反的等位基因上携带第二个HIT R130X突变，这两个突变都在CS和ERR中被描述过。我们推测第二次命中。R130X在胚胎发育早期出现，ANA甚至可能代表种系嵌合体。因此，PTEN可能参与Proteus样综合征及其对未来癌症发展的影响。
Germline PTEN mutations cause Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRR), two harmatoma-tumour syndromes, and somatic PTEN alterations have been shown to participate, to a greater or lesser extent, in a wide variety of sporadic neoplasia. PTEN is a tumour suppressor and dual-specificity phosphatase which affects apoptosis via its lipid phosphatase activity in the phosphoinositol-3-kinase and AKT pathway as well as inhibiting cell spreading via the focal adhesion kinase pathway. CS and ERR share some features, such as hamartomas and lipomatosis, To determine whether other syndromes characterized by overgrowth and lipomas are part of the PTEN syndrome spectrum, we ascertained six individuals with overgrowth and lipomas but who did not meet the diagnostic criteria for CS or ERR. Five had Proteus syndrome and one, a Proteus-like syndrome. When germline DNA and DNA from at least one involved tissue per case were examined for PTEN mutations, only the Proteus-like patient was found to harbour a germline R335X mutation. Interestingly, a lipomatous mass, an epidermoid naevus and arteriovenous malformation tissue, all of which were sampled from physically distinct sites, were all found to carry a second hit R130X mutation on the allele opposite the germline R335X, Both mutations have been described in CS and ERR. We postulate that the second hit. R130X, occurred early in embryonic development ana may even represent germline mosaicism. Thus, PTEN may be involved in Proteus-like syndrome with its implications for cancer development in the future.