Activation of cyclic AMP signaling leads to different pathway alterations in lesions of the adrenal cortex caused by germline PRKAR1A defects versus those due to somatic GNAS mutations

PRKAR1A inactivating mutations are responsible for primary pigmented nodular adrenocortical disease (PPNAD) whereas somatic GNAS activating mutations cause macronodular disease in the context of McCune-Albright syndrome (MAS), ACTH-independent hyperplasia (AIMAH) and, rarely, cortisol-producing adenomas (CPA). The whole-genome expression profile (WGEP) of normal (pooled) adrenals, PRKAR1A- (3) and GNAS-mutant (3) was studied. Total RNA obtained from adrenal tumors were compared to those samples obtained from normal adrenal pools

PRKAR1A失活突变可引发原发性色素性结节状肾上腺皮质病 (primary pigmented nodular adrenocortical disease, PPNAD)；体细胞GNAS激活突变则会在McCune-Albright综合征 (McCune-Albright syndrome, MAS)、促肾上腺皮质激素非依赖性增生 (ACTH-independent hyperplasia, AIMAH) 以及罕见的皮质醇腺瘤 (cortisol-producing adenomas, CPA) 的背景下导致大结节性肾上腺疾病。本研究对正常（混合池）肾上腺、PRKAR1A失活突变型（3例）及GNAS激活突变型（3例）样本的全基因组表达谱 (whole-genome expression profile, WGEP) 开展了分析，并将肾上腺肿瘤样本提取的总RNA与正常肾上腺混合池样本进行了对照比较。