Integrating Methylome and Transcriptome Signatures Expands the Molecular Classification of the Pituitary Tumors
Authors' conclusion
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 definition 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.
Study context
- Population
- Patients with functioning and nonfunctioning pituitary tumors, heterogeneous ethnic Brazilian population, Ribeirao Preto Medical School, University of São Paulo; 61% women, age 12–72 yearstranscriptome n = 65
- Participants
- 77 patients
- Exposure
- GH-secreting vs ACTH-secreting vs nonfunctioning pituitary tumors (NFPT)
- GH-secretingn = 18
- ACTH-secretingn = 14
- NFPTn = 45
- Outcome
- Unsupervised hierarchical clustering of:
- Methylome
- Transcriptome
Methodological detailssingle-centre
- Single-centre
Main finding
As reported in the abstract
Clusters revealed by unsupervised hierarchical clustering analysis (UHCA) of methylome (n = 77) and transcriptome (n = 65) each: one enriched by FPT, one by NFPT, a third by ACTH-secreting and NFPT
3
Differentially methylated genes between omics-derived clusters
3568
Differentially expressed genes between omics-derived clusters
5994
Observational data: associations, not effects.
Further findings
UHCA of 11 transcripts related to pituitary development/differentiation
- Clusters: POU1F1-driven somatotroph, TBX19-driven corticotroph and NR5A1-driven gonadotroph adenomas
- 3
- Rare exceptions: NR5A1 in few GH-secreting and corticotroph silent adenomas; POU1F1 in few ACTH-secreting adenomas; TBX19 in few NFPTs
Original publication
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