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DNA methylation pattern in somatotroph pituitary neuroendocrine tumors

ABSTRACT: Secretion of growth hormone by sporadic somatotroph neuroendocrine pituitary tumors (PitNETs) is the most common cause of acromegaly.Genome-wide DNA methylation was investigated in 48 somatotroph PitNETs with EPIC microarrays. Three subtypes of the tumors were identified. Subtype 1 tumors are densely granulated tumors without GNAS mutation characterized by high expression of NR5A1 (SF-1) and GIPR. The expression of both genes is correlated with specific methylation pattern at gene body and promoter methylation. Subtype 1 has generally lower methylation level at 5’ gene regulatory regions and CpG islands as compared to other tumor clusters. Subtype 2 are densely granulated PiNETs with common GNAS-mutations while Subtype 3 are mainly sparsely granulated tumors. Methylation/expression analysis indicate that the levels of ~50% genes differentially expressed genes between tumor subtypes that are located at in differentially methylated regions are DNA methylation dependent. These DNA methylation-controlled genes include CDKN1B, CCND2, EBF3, CDH4, CDH12 MGMT, STAT5A, PLXND1, PTPRE and MMP16 as wells as genes encoding ion channels and semaphorins. Results of DNA methylation profiling confirms three molecular subtypes of somatotroph PitNETs that differ in both gene expression and methylation pattern. High expression of NR5A1 and GIPR in subtype 1 tumors is correlated to specific methylation at both genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE226764 | GEO | 2023/09/25

REPOSITORIES: GEO

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