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Fjeldbo, C. S.

Publications and source records attributed to Fjeldbo, C. S..

2 recordsLinked to original sources

Analysis of patient data reveals novel cancer-relevant functions for GCN2/eIF2αK4

Numerous studies have shown that high GCN2 levels correlate with poor survival in a number of cancers. GCN2 has been known for over thirty years as a stress-response kinase, which phosphorylates the translation-initiation factor eIF2, and thereby contributes to reprogramming of translation. Here we performed correlation analyses of GCN2 expression and that of other genes in a patient-derived sample set of cervical cancer samples. We found correlations not only with genes involved in stress responses, but also with genes involved in mitosis and cell migration. Our functional analyses confirmed that these correlations indeed reveal novel functions. Furthermore, our analyses of growth benefits associated with elevated GCN2 levels suggest that the novel functions can contribute to aggressive disease in cancers with high GCN2 levels.

cell biology↗

Pro-metastatic gene expression, immune evasion and an altered HPV spectrum characterize an aggressive subtype of cervical cancer

Human papillomavirus (HPV)-associated cervical cancer represents one of the leading causes of cancer death worldwide. Although low-middle income countries are disproportionately affected, our knowledge of the disease predominantly originates from populations in high-income countries. Using the largest multi-omic analysis of cervical squamous cell carcinoma (CSCC) to date, totalling 643 tumours and representing patient populations from the USA, Europe and Sub-Saharan Africa, we identify two CSCC subtypes (C1 and C2) with differing prognosis. C1 tumours are largely HPV16-driven, display increased cytotoxic T-lymphocyte infiltration and frequently harbour PIK3CA and EP300 mutations. C2 tumours are associated with shorter overall survival, are frequently driven by HPVs from the HPV18-containing alpha-7 clade, harbour alterations in the Hippo signalling pathway and increased expression of immune checkpoint genes, B7-H3 (also known as CD276) and NT5E (also known as CD73) and PD-L2 (also known as PDCD1LG2). In conclusion, we identify two novel, therapy-relevant CSCC subtypes that share the same defining characteristics across three geographically diverse cohorts.

cancer biology↗