Detection of genes with recurrent pathogenic somatic mutation in aldosterone-producing adenomas through whole exome sequencing (WES)

Whole exome sequencing of aldosterone-producing adenomas (APAs) and paired adjacent adrenal from primary aldosteronism (PA) patients was conducted with previously genotyped controls (n=3 in each centre/institute) as validation of sensitivity. MuTect2 analysis was conducted in order to identify adrenocortical genes with somatic mutations, predicted by Sorting Intolerant from Tolerant (SIFT) and Polymorphism Phenotyping (PolyPhen)-2 to be functional. Candidate mutations were confirmed by Sanger sequencing of DNA from fresh samples of the APA, and sought in other previously genotyped APAs that were not included in the WES.