MON-017 Single-cell Transcriptomic Profiling of Somatotroph Tumors Reveals Subtype-Specific Cellular and Molecular Characteristics

Abstract Disclosure: E. Kim: None. H. Oh: None. C. Ku: None. While single-cell profiling has been extensively explored in various tumor types, pituitary adenomas, particularly somatotroph tumors (ST), remain understudied. These growth hormone-secreting adenomas are clinically classified into two subtypes, Densely Granulated (DG) and Sparsely Granulated (SG), which have distinct prognostic implications. However, the cellular and molecular differences between these subtypes at the single-cell level are poorly understood. In this study, we performed single-cell RNA sequencing (scRNA-seq) on 12 somatotroph tumor samples, comprising 52,310 cells prospectively collected from acromegaly patients (10 DG and 2 SG). For the first time, we delineated tumor subclustering within ST, identifying two major populations: classic somatotroph (classic ST) and neuronal-like clusters (neuronal ST). A comparison of DG and SG subtypes revealed significant differences in immune cell composition, with DG tumors harboring higher proportions of myeloid and lymphoid lineage cells. Gene set enrichment analysis (GSEA) further highlighted the upregulation of immune-related pathways, including TNF-alpha signaling, in the DG subtype. These findings were validated by immunohistochemistry (IHC). Additionally, prolactin (PRL) expression was markedly elevated in DG tumors compared to SG tumors. A distinct population of cells co-expressing growth hormone (GH1) and PRL was identified, exclusively present in the DG subtype, and corroborated by IHC. Finally, copy number variation (CNV) analysis revealed substantial genomic instability within ST. Notably, most ST cells exhibited high CNV in the chromosome 20p arm within the classic ST cluster, while the neuronal ST cluster of the SG subtype displayed more prominent high CNV in the 20q arm compared to the DG subtype. This study represents the first single-cell transcriptomic analysis of somatotroph tumors, uncovering key cellular and molecular features that differentiate DG and SG subtypes. These findings provide new insights into tumor classification and hold significant potential for the development of targeted therapies. Presentation: Monday, July 14, 2025