HIF1A P582S

Furthermore, HIF1A expression significantly correlated (P-value < .000001) with hypoxia, TMB, MSI, and immune infiltration by CD8+ T cells, neutrophils, dendritic, and macrophages, providing deeper insights into the BC microenvironment. Thus, the HIF1A gene could serve as a promising biomarker for breast cancer progression, control, and survival across ethnicities, emphasizing its role in disease development and regulation.

We identified recurrent germline variants in 42 (75%) patients occurring mainly in JAK/STAT, Hypoxia and Iron metabolism pathways, among them: JAK3-V722I and HIF1A-P582S; a high fraction of patients (48.2%) resulted also mutated in homeostatic iron regulatory gene HFE-H63D or C282Y. By generating cellular models, we showed that JAK3-V722I causes activation of the JAK-STAT5 axis and upregulation of EPAS1/HIF2A, while HIF1A-P582S causes suppression of hepcidin mRNA synthesis, suggesting a major role for these variants in the onset of IE.

Common SNPs in genes regulating glucose uptake may impact SUV, tumour distribution, tumour volume, and outcome in DLBCL. The effects on SUV are of low magnitude and appear clinically negligible. The results are consistent with findings in other types of cancer. They need to be confirmed in an independent DLBCL population of sufficient size.