Next-generation sequencing in the clinical genetic screening of patients with pheochromocytoma and paraganglioma

被引：35

作者：

Crona, Joakim ^{[1
]}

Verdugo, Alberto Delgado ^{[1
]}

Granberg, Dan ^{[2
]}

Welin, Staffan ^{[2
]}

Stalberg, Peter ^{[1
]}

Hellman, Per ^{[1
]}

Bjorklund, Peyman ^{[1
]}

机构：

[1] Uppsala Univ, Dept Surg Sci, S-75185 Uppsala, Sweden

[2] Uppsala Univ, Dept Med Sci, S-75185 Uppsala, Sweden

来源：

ENDOCRINE CONNECTIONS | 2013年 / 2卷 / 02期

关键词：

exome sequencing; whole genome sequencing; pheochromocytoma; paraganglioma; MEDULLARY-THYROID CARCINOMA; WHOLE-EXOME; NF1; GENE; MUTATIONS; PREVALENCE; DISCOVERY; DIAGNOSIS; VARIANTS; SPECTRUM; BENIGN;

D O I：

10.1530/EC-13-0009

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Recent findings have shown that up to 60% of pheochromocytomas (PCCs) and paragangliomas (PGLs) are caused by germline or somatic mutations in one of the 11 hitherto known susceptibility genes: SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, HIF2A (EPAS1), RET, NF1, TMEM127 and MAX. This list of genes is constantly growing and the 11 genes together consist of 144 exons. A genetic screening test is extensively time consuming and expensive. Hence, we introduce next-generation sequencing (NGS) as a time-efficient and cost-effective alternative. Methods: Tumour lesions from three patients with apparently sporadic PCC were subjected to whole exome sequencing utilizing Agilent Sureselect target enrichment system and Illumina Hi seq platform. Bioinformatics analysis was performed in-house using commercially available software. Variants in PCC and PGL susceptibility genes were identified. Results: We have identified 16 unique genetic variants in PCC susceptibility loci in three different PCC, spending less than a 30-min hands-on, in-house time. Two patients had one unique variant each that was classified as probably and possibly pathogenic: NF1 Arg304Ter and RET Tyr791Phe. The RET variant was verified by Sanger sequencing. Conclusions: NGS can serve as a fast and cost-effective method in the clinical genetic screening of PCC. The bioinformatics analysis may be performed without expert skills. We identified process optimization, characterization of unknown variants and determination of additive effects of multiple variants as key issues to be addressed by future studies.

引用

页码：104 / 111

页数：8

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