Results for “region 11p15.5”

PubMed2025

The genetic changes in 11p15.5-related pheochromocytomas and paragangliomas.

Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors. The development of these tumors is associated with more than 20 genes. The aforementioned genes are subdivided into three clusters. The pseudohypoxic, kinase-signaling and Wnt clusters. The pseudohypoxic cluster is the only one that has been demonstrated to be associated with DNA methylation changes, including alterations in the 11p15.5 region. The objective of this study was to identify alterations in the 11p15.5 region, ascertain their prevalence in PPGLs, and subsequently compare them with the genomic and somatic mutations that cluster PPGLs. One hundred and fifty tumor samples were subjected to analysis. A total of 90 cases (60%) exhibited no alterations in the 11p15.5 region. The most prevalent alterations were maternal allele loss, observed in 45 cases (30%), pUPD (paternal uniparental disomy) in five cases (3.33%), and paternal allele gain in four cases (2.67%). The data presented here suggest that two mechanisms may be involved in the formation of PPGLs. These are reduced expression of CDKN1C (maternal allele deletion) and overexpression of IGF2 (pUPD, paternal allele gain). A statistically significant difference was observed in the frequency of alterations in the 11p15.5 region when comparing cluster 1 and cluster 2 (P-value <0.0001). This study is the first to describe pUPD and paternal allele gain as somatic alterations in PPGLs. In addition, our findings indicate that alterations in the 11p15.5 region are not exclusive to cluster 1. Consequently, the alterations in the 11p15.5 region cannot be regarded as a marker for cluster 1.

Humans↗

PubMed2026

A regulatory network underlying idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease in which genetic susceptibility interacts with epithelial, immune, and mesenchymal remodeling. Although the chromosome 11p15.5 locus contains established IPF susceptibility signals near MUC5B and TOLLIP, the broader regulatory architecture of this region remains incompletely resolved. METHODS: We integrated IPF genome-wide association study summary statistics with methylation, expression, and protein quantitative trait loci using summary-data-based Mendelian randomization (SMR). SMR-prioritized candidates were evaluated in independent transcriptomic and methylation cohorts and further contextualized using microRNA, transcription-factor, protein-interaction, machine-learning, single-cell, and spatial transcriptomic analyses. Fibrosis-associated expression patterns were assessed in a bleomycin-induced pulmonary fibrosis rat model. RESULTS: The analyses recovered the established MUC5B and TOLLIP signals and prioritized BRSK2 as a comparatively underexplored candidate supported by eQTL-based SMR and independent molecular evidence. The BRSK2 pQTL association did not pass the HEIDI test and was therefore not interpreted as convergent protein-level genetic evidence. Network analyses linked BRSK2 to cell-cycle, metabolic-stress, and senescence-related programs, while cross-cohort machine learning prioritized FOXA2, CDC25B, and NFE2 as informative network features. Single-cell and spatial analyses localized BRSK2 preferentially to fibroblast and myofibroblast compartments and to regions with greater histological fibrosis severity. In fibrotic rat lungs, BRSK2 expression increased, whereas FOXA2 and CDC25B decreased at the transcript and protein levels. CONCLUSIONS: These findings refine the molecular landscape of the chromosome 11p15.5 IPF susceptibility locus and prioritize BRSK2 as a candidate component of an IPF-associated profibrotic fibroblast state. Its causal contribution, direct regulatory relationships, and therapeutic tractability require targeted mechanistic validation.

Idiopathic Pulmonary Fibrosis↗