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In this study, we aimed to integrate the genetic alterations, protein expression profiles, transcriptomes, and clinical characteristics of GHomas\/somatotroph PitNETs to identify molecules associated with acromegaly characteristics. Targeted capture sequencing and copy number analysis of 36 genes and nontargeted proteomics analysis were performed on fresh-frozen samples from 121 sporadic GHomas\/somatotroph PitNETs. Targeted capture sequencing revealed\n                    <jats:italic>GNAS<\/jats:italic>\n                    as the only driver gene, as previously reported. Classification by consensus clustering using both RNA sequencing and proteomics revealed many similarities between the proteome and the transcriptome. Gene ontology analysis was performed for differentially expressed proteins between wild-type and mutant\n                    <jats:italic>GNAS<\/jats:italic>\n                    samples identified by nontargeted proteomics and involved in G protein\u2013coupled receptor (GPCR) pathways. The results suggested that\n                    <jats:italic>GNAS<\/jats:italic>\n                    mutations impact endocrinological features in acromegaly through GPCR pathway induction. ATP2A2 and ARID5B correlated with the GH change rate in the octreotide loading test, and WWC3, SERINC1, and ZFAND3 correlated with the tumor volume change rate after somatostatin analog treatment. These results identified a biological connection between\n                    <jats:italic>GNAS<\/jats:italic>\n                    mutations and the clinical and biochemical characteristics of acromegaly, revealing molecules associated with acromegaly that may affect medical treatment efficacy.\n                  <\/jats:p>","DOI":"10.1038\/s42003-022-04272-1","type":"journal-article","created":{"date-parts":[[2022,11,27]],"date-time":"2022-11-27T06:28:12Z","timestamp":1669530492000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Proteogenomic landscape and clinical characterization of GH-producing pituitary adenomas\/somatotroph pituitary neuroendocrine 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