RT Journal Article SR Electronic T1 Targeted next-generation sequencing detects rare genetic events in pheochromocytoma and paraganglioma JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 513 OP 520 DO 10.1136/jmedgenet-2018-105714 VO 56 IS 8 A1 Laurène Ben Aim A1 Pascal Pigny A1 Luis Jaime Castro-Vega A1 Alexandre Buffet A1 Laurence Amar A1 Jérôme Bertherat A1 Delphine Drui A1 Isabelle Guilhem A1 Eric Baudin A1 Charlotte Lussey-Lepoutre A1 Carole Corsini A1 Gérard Chabrier A1 Claire Briet A1 Laurence Faivre A1 Catherine Cardot-Bauters A1 Judith Favier A1 Anne-Paule Gimenez-Roqueplo A1 Nelly Burnichon YR 2019 UL http://jmg.bmj.com/content/56/8/513.abstract AB Background Knowing the genetic status of patients affected by paragangliomas and pheochromocytomas (PPGL) is important for the guidance of their management and their relatives. Our objective was to improve the diagnostic performances of PPGL genetic testing by next-generation sequencing (NGS).Methods We developed a custom multigene panel, which includes 17 PPGL genes and is compatible with both germline and tumour DNA screening. The NGS assay was first validated in a retrospective cohort of 201 frozen tumour DNAs and then applied prospectively to 623 DNAs extracted from leucocytes, frozen or paraffin-embedded PPGL tumours.Results In the retrospective cohort, the sensitivity of the NGS assay was evaluated at 100% for point and indels mutations and 86% for large rearrangements. The mutation rate was re-evaluated from 65% (132/202) to 78% (156/201) after NGS analysis. In the prospective cohort, NGS detected not only germline and somatic mutations but also co-occurring variants and mosaicism. A mutation was identified in 74% of patients for whom both germline and tumour DNA were available.Conclusion The analysis of 824 DNAs from patients with PPGL demonstrated that NGS assay significantly improves the performances of PPGL genetic testing compared with conventional methods, increasing the rate of identified mutations and identifying rare genetic mechanisms.