# Genetic alterations and aberrant hormonal pathways in thymic epithelial tumors

## TL;DR

This study identifies genetic changes and hormone-related pathways in thymic epithelial tumors, highlighting RHPN2 as a key gene linked to survival and paraneoplastic syndromes.

## Contribution

The study reveals RHPN2 as a frequently mutated gene in TETs and links it to hormone pathways and poorer patient survival.

## Key findings

- Mutated genes in TETs are enriched in hormone-associated and tumor-related pathways like insulin secretion and WNT signaling.
- RHPN2 is the most frequently mutated gene in TETs and is associated with upregulated hormone pathways and shorter patient survival.
- Patients with paraneoplastic syndromes show more pronounced alterations in hormone-related pathways.

## Abstract

Patients with thymic epithelial tumors (TETs) frequently show coexistence of various paraneoplastic syndromes, which severely affect their survival. Moreover, there is a lack of effective clinical treatment strategies for patients with unresectable metastatic and recurrent TETs.

To explore the genetic alterations that play a key role in the pathogenesis of TETs, we analyzed the whole-exome sequencing data from 24 patients diagnosed to have TETs at the First Affiliated Hospital of Nanjing Medical University.

Mutated genes in TETs were enriched in several hormone-associated pathways such as insulin secretion; Cushing syndrome; parathyroid hormone; and thyroid hormone, as well as multiple classical tumor-associated pathways, including cAMP, Notch, PI3K-Akt, and WNT signaling pathway. Patients with paraneoplastic syndromes (PNS) exhibited more pronounced alterations in hormone-related pathways. RHPN2 is the most frequently mutated gene in TETs. TETs with RHPN2 mutation showed greater upregulation of the hormone-related signaling pathways such as thyroid hormone and parathyroid hormone as well as a trend toward shorter survival of patients.

We analyzed the possible role of hormones in TETs on several levels, explored potential links between hormones and other genetic mutations, and found that RHPN2 may be a potentially valuable gene.

The online version contains supplementary material available at 10.1186/s12885-025-15455-4.