Novel SDHB and TMEM127 Mutations in Patients with Pheochromocytoma/Paraganglioma Syndrome

Pathology & Oncology Research

Geza Toth⁶  Miklos Toth¹  Vince K Grolmusz²  Istvan Liko⁴  Henriett Butz⁷  Peter Igaz¹  Károly Rácz³  Attila Patócs⁵  Nikolette Szucs¹  Zoltan Sapi¹  Nikoletta K. Lendvai² 

[1] Semmelweis University$$;Hungarian Academy of Sciences and Semmelweis University$$Semmelweis University$$;Bionics Innovation Center$$Semmelweis University$$Hungarian Academy of Sciences and Semmelweis University$$;Hungarian Academy of Sciences and Semmelweis University$$;Hungarian Academy of Sciences and Semmelweis University$$Bionics Innovation Center$$Semmelweis University$$;Ferenc Markhot County Hospital$$;Hungarian Academy of Sciences and Semmelweis University$$Hungarian Academy of Sciences and Semmelweis University$$

关键词: Genotype-phenotype;   

DOI  :  10.1007/s12253-016-0050-0

学科分类：生理学与病理学

来源: Springer

【 摘 要 】

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 with SDHB mutations. Our aim was to determine the prevalence of germline SDHx, SDHAF2, MAX and TMEM127 mutations in Hungarian patients with apparently sporadic Pheo/PGLs. Mutation screening of the SDHx, SDHAF2, MAX and TMEM127 genes 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 4 SDHB and 2 TMEM127 mutations were novel. Earlier development of Pheo/PGL, more malignant phenotype and multiple tumors were observed in genetically positive cases especially in those with SDHB mutations. The presence of bilateral or multiple tumors was the most predictive for identification of a pathogenic mutation. Together with cases harboring germline RET, VHL and NF1 mutations, 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.

【 授权许可】

Unknown