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Purpose: To explore pituitary tumors by methylome and transcriptome
signatures in a heterogeneous ethnic population. Design: Retrospective
cross-sectional study. Patients and Methods: Clinicopathological features,
methylome, and transcriptome were evaluated in pituitary tumors from
77 patients (61% women, age: 12-72 years)followed due to functioning
(FPT: GH-secreting n=18, ACTH-secreting n=14) and non-functioning
pituitary tumors (NFPT, n=45) at Ribeirao Preto Medical School, University
of Sao Paulo. Results: Unsupervised hierarchical clustering analysis
(UHCA) of methylome (n=77) and transcriptome (n=65 out of 77) revealed
three clusters each: one enriched by FPT, other by NFPT, and another
by ACTH-secreting and NFPT. Comparison between each omics-derived cluster
identified 3,568 and 5,994 differentially methylated and expressed genes,
respectively, which were associated with each other, with tumor clinical
presentation, and with 2017 and 2022 WHO classifications. UHCA considering
11 transcripts related to pituitary development/differentiation
also supported three clusters: POU1F1-driven
somatotroph, TBX19-driven corticotroph, and NR5A1-driven gonadotroph
adenomas, with rare exceptions (NR5A1 expressed in few GH-secreting and
corticotroph-silent adenomas; POU1F1 in few ACTH-secreting adenomas;
and TBX19 in few NFPTs). Conclusions: This large heterogenic ethnic
Brazilian cohort confirms that integrated methylome and transcriptome
signatures classify FPT and NFPT, which are associated with clinical
presentation and tumor invasiveness. Moreover, the cluster
NFPT/ACTH-secreting adenomas raises interest regarding tumor
heterogeneity, supporting the challenge raised by the 2017 and 2022 WHO
definitions regarding the discrepancy, in rare cases, between clinical
presentation and pituitary lineage markers. Finally, making our data
publicly available enables further studies to validate genes/pathways
involved in pituitary tumor pathogenesis and prognosis.
176 views reported since publication in 2022.