Pituitary adenomas (PAs) are one of the most common intracranial tumors, which can result in significant morbidity and can cause mortality either by exerting central pressure effects from the pituitary mass or by secreting excessive pituitary hormones [1]. Depending on their capability to produce hormones, PAs are classified as clinically functioning and nonfunctioning (NF). Functioning PAs include 6 subtypes, characterized by hypersecretion of prolactin (PRL), growth hormone (GH), adrenocorticotropin (ACTH), gonadotropins including follicle stimulating hormone and luteinizing hormone (GT), thyrotropin (TSH) or multiple hormones (plurihormonal), respectively. We and other group recently reported the recurrent genetic mutations in ACTH-PAs [2, 3]. Previous studies also identified genetic alterations in GH-PAs by wholegenome and-exome sequencing [4, 5] and in 7 NF-PAs by exome analysis [6]. Due to challenges in collection and preparation of PA samples, exome-wide sequencing of other subtypes, including the PRL-, GT-, TSH-, and plurihormonal PA subtypes, has not been reported yet. To provide a comprehensive genetic landscape of all 7 subtypes of PAs, we examined the somatic mutational landscape of 125 PAs, including 20 NF-PAs, 20 PRL-PAs, 20 GH-PAs, 20 ACTH-PAs, 20 GT-PAs, 10 TSH-PAs, and 15 plurihormonal PAs. Plurihormonal PAs in this series secreted GH+ PRL (n= 11), GH+ ACTH (n= 2), or GH+ TSH (n= 2). The analysis of 20 ACTH-PAs included 12 tumor samples analyzed in our previous study [2]. The clinical characteristics of these patients are summarized in Supplementary information, Table S1A. The detailed methods are described in Supplementary information, Data S1 and Figure S1A. We identified 412 somatic mutations in 125 PAs (Supplementary information, Table S1B). This analysis confirmed a relatively low number of somatic mutations per tumor across all 7 PA subtypes (mean= 3.3 mutations per exome; Figure 1A)[3-6]. The predominant substitution was C> T/G> A transitions which accounted for 41% of all substitutions across all PA subtypes, followed by T> C/A> G transitions (23%), similar to other intracranial tumors (Supplementary information, Figure S1B). Recurrently-mutated genes are shown in Figure 1A.