Exome sequencing in phaeochromocytoma/paraganglioma

Phaeochromocytomas (PCC) and paragangliomas (PGL) are tumours arising from the adrenal medulla or from extra-adrenal sympathetic or parasympathetic paraganglia. Genetic testing is recommended when the probability of a disease-associated germline mutation exceeds 10%. Germline mutations are found in approximately 25% of individuals with PCC or PGL; however, genetic heterogeneity for PCC/PGL means many genes may require sequencing increasing both time and cost of diagnosis.

In this study, McInerney-Leo et al. have assessed whether whole exome sequencing (WES), using an off-the-shelf exome capture platform rather than designing individual targeted assays, is a sensitive, time- efficient and cost-effective way to offer genetic testing in a population of individuals with established diagnosis of PCC/PGL. They also evaluated the target capture of the currently available exome capture platforms for exons of the known PCC/PGL genes.

They demonstrate that WES accurately diagnosed all mutations in all 11 patients with PCC/PGL in whom mutations had been detected previously by Sanger sequencing. Further, they were able to discriminate between disease-associated mutations and irrelevant variants. However, they caution that appropriate choice of capture platform is critical to ensure adequate coverage of all exons of known PCC/PGL genes.

Read the full article at McInerney-Leo et al. (2014) Clinical Endocrinology 80; 25-33; DOI: 10.1111/cen.12331