Novel SDHB and TMEM127 Mutations in Patients with Pheochromocytoma/Paraganglioma Syndrome
Novel SDHB and TMEM127 Mutations in Patients with Pheochromocytoma/Paraganglioma Syndrome
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DOI：
10.1007/s12253-016-0050-0
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发表时间：
2016-03
影响因子：
2.8
通讯作者：
A. Patócs;N. Lendvai;H. Butz;I. Likó;Z. Sápi;N. Szűcs;G. Tóth;V. Grolmusz;P. Igaz;M. Tóth;K. Rácz
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文献类型：
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作者：
A. Patócs;N. Lendvai;H. Butz;I. Likó;Z. Sápi;N. Szűcs;G. Tóth;V. Grolmusz;P. Igaz;M. Tóth;K. Rácz
嗜铬细胞瘤（Pheo）和副神经节瘤（PGL）是罕见的肿瘤，具有异质性的遗传背景。在所有明显散发的Pheo/PGL病例中，可在代表Pheo/PGL遗传易感性的15个基因之一中鉴定出种系突变，占30%。恶性肿瘤是罕见的，但它经常与sdhb突变有关。我们的目的是确定种系esdhx、SDHAF2、maxand tmem127突变在匈牙利明显散发的Pheo/ pgl患者中的流行程度。采用PCR和双向Sanger测序技术，对82例匈牙利明显散发型Pheo/PGL患者进行了theSDHx、SDHAF2、maxandtmem127基因的突变筛选。在11例患者中鉴定出致病种系突变，其中4SDHBand 2tmem127突变是新发现的。在基因阳性的病例中，特别是在sdhb突变的病例中，观察到Pheo/PGL的早期发展，更多的恶性表型和多发性肿瘤。双侧或多发肿瘤的存在是鉴定致病性突变最具预测性的。匈牙利Pheo/PGL患者与携带种系eret、vhlandnf1突变的病例一起，表现出异质突变谱，表明应检测所有Pheo/PGL易感基因。本研究揭示的新的基因型-表型关联可能有助于改进诊断方法，并有助于实现对Pheo/PGL患者更好的临床随访。
Pheochromocytomas (Pheo) and paragangliomas (PGL) are rare tumors, with heterogeneous genetic background. In up to 30 % of all, apparently sporadic Pheo/PGL cases germline mutations can be identified in one of the 15 genes representing genetic susceptibility for Pheo/PGL. Malignancy is rare but it frequently associates withSDHBmutations. Our aim was to determine the prevalence of germlineSDHx,SDHAF2,MAXandTMEM127mutations in Hungarian patients with apparently sporadic Pheo/PGLs. Mutation screening of theSDHx,SDHAF2,MAXandTMEM127genes was performed in 82 Hungarian patients with apparently sporadic Pheo/PGL using PCR and bidirectional Sanger sequencing. Disease-causing germline mutations were identified in 11 patients, of which 4SDHBand 2TMEM127mutations were novel. Earlier development of Pheo/PGL, more malignant phenotype and multiple tumors were observed in genetically positive cases especially in those withSDHBmutations. The presence of bilateral or multiple tumors was the most predictive for identification of a pathogenic mutation. Together with cases harboring germlineRET,VHLandNF1mutations, Hungarian patients with Pheo/PGL exhibit a heterogeneous mutation spectrum, indicating that all of the Pheo/PGL susceptibility genes should be tested. Novel genotype-phenotype associations revealed by our study may contribute to improvement of diagnostic approaches and may help to achieve a better clinical follow up for patients with Pheo/PGL.