Fig 2: Panel (a,b) show the circos plot of the differentially mRNA expressed genes (inner circle), the chromosome (middle circle) and the proteins (outer circle) related to Spliceosome machinery or splicing events in NR5A1- and POU1F1-derived pituitary tumors, respectively.

Fig 3: (A) Methylome PCA of the three pituitary adenoma clusters: POU1F1-driven somatotropinoma-thyrotropinoma-prolactinoma cluster; NR5A1-driven gonadotropinoma and null cell adenoma cluster; and TBX19-driven adrenocorticotropinoma cluster. Silent ACTH-adenomas segregated separately between TBX19-adenomas and NR5A1-adenomas. (B) Differentially methylated genes heatmap clustering POU1F1-derived adenomas, NR5A1-derived adenomas and TBX19-adenomas which split in two groups, one cluster next to POU1F1 adenomas and the second next to NR5A1 adenomas. The “Y” axis represents the tumor sample clustering according to WHO 2017 classification, as well as clinical features such as size, invasion, recurrence and aggressiveness, while the “X” axis represents the methylated regions hierarchical cluster. Image was created using Partek Genomics Suite 7.19v (https://www.partek.com/partek-genomics-suite/).

Fig 4: Representative deregulated pathways in the TBX19-, POU1F1- and NR5A1-derived tumors. Altered cellular events cluster the tumors into the respective transcription factors they derive from. Silent ACTH tumors resemble the NR5A1-driven cells more than the TBX19-driven cells and therefore share molecular events common to both cell lineages. CA = control, non-tumoral gland, which has a PDS of 0; AC = GH tumors causing acromegaly; NC = clinically non-functioning null cell adenomas; CU = ACTH tumors causing Cushing’s disease; GO = gonadotropin tumors causing clinically non-functioning adenomas; SA = silent ACTH, clinically non-functioning tumors; PRL = prolactin-secreting prolactinomas; TI = TSH-secreting tumors or thyrotropinomas.

Fig 5: Panel (a–c) denotes the altered cellular events in which total proteins participates in NR5A1- and POU1F1-derived pituitary tumors and total detected proteins in control glands, respectively.