Analysis of polymorphisms in EGF, EGFR and HER2 genes in pancreatic neuroendocrine tumors (PNETs)

Marinović, Sonja; Berković, Maja Cigrovski; Zjačić-Rotkvić, Vanja; Kapitanović, Sanja

doi:10.1016/j.cancergen.2022.06.005

Cited by 5 publications

(4 citation statements)

References 46 publications

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“…Then, we performed gene set enrichment analysis to further identify the key molecular mechanisms that have been altered by the genetic alterations. Consistent with previously published studies [ 19 , 20 , 21 ], we found pathways in cancer were significantly affected in PanNETs and liver metastases, and that EGFR tyrosine kinase inhibitor resistance and transcriptional misregulation in cancer were unique to liver metastases via KEGG pathway analysis; simultaneously, GO Biological Processes analysis underlined those signaling pathways tightly related to tyrosine phosphorylation, DNA repair, and cell cycle regulation, especially in liver metastases ( Table 3 , Supplementary Table S1 ).…”

Section: Resultssupporting

confidence: 91%

Evolutionary Trajectories of Primary and Metastatic Pancreatic Neuroendocrine Tumors Based on Genomic Variations

Yan

et al. 2022

Genes

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Liver metastases are common in pancreatic neuroendocrine tumors (PanNETs) patients and they are considered a poor prognostic marker. This study aims to analyze the spatiotemporal patterns of genomic variations between primary and metastatic tumors, and to identify the key related biomolecular pathways. We performed next-generation sequencing on paired tissue specimens of primary PanNETs (n = 11) and liver metastases (n = 12). Low genomic heterogeneity between primary PanNETs and liver metastases was observed. Genomic analysis provided evidence that polyclonal seeding is a prevalent event during metastatic progression, and may be associated with the progression-free survival. Besides this, copy number variations of BRCA1/BRCA2 seem to be associated with better prognosis. Pathways analysis showed that pathways in cancer, DNA repair, and cell cycle regulation-related pathways were significantly enriched in primary PanNETs and liver metastases. The study has shown a high concordance of gene mutations between the primary tumor and its metastases and the shared gene mutations may occur during oncogenesis and predates liver metastasis, suggesting an earlier onset of metastasis in patients with PanNETs, providing novel insight into genetic changes in metastatic tumors of PanNETs.

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Section: Resultssupporting

confidence: 91%

Evolutionary Trajectories of Primary and Metastatic Pancreatic Neuroendocrine Tumors Based on Genomic Variations

Yan

et al. 2022

Genes

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“…In that case, the identification of additional, potential NET-subtype specific, growth-factor dependencies could enable the generation of PDTO models of additional NETs subtypes, such as ileal NETs, which we were not able to propagate long-term. Consistent with this idea, a recent report found that certain polymorphisms in EGFR were associated with increased risk of developing pancreatic NET (Marinović et al, 2022). Beyond model generation, the identification of growth-factor dependencies for these and other tumors could lead to the identification of new therapeutic strategies aimed at targeting growth-factor mediated pathways in specific patient populations.…”

Section: Experimental Models For Low-grade Tumorsmentioning

confidence: 84%

Druggable Growth Dependencies and Tumor Evolution Analysis in Patient-Derived Organoids of Neuroendocrine Cancer

Dayton

Alcala

Moonen

et al. 2022

Preprint

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Neuroendocrine neoplasms (NENs) comprise well-differentiated neuroendocrine tumors and poorly-differentiated carcinomas. Treatment options for patients with NENs are limited, in part due to lack of accurate models. To address this need we established the first patient-derived tumor organoids (PDTOs) from pulmonary neuroendocrine tumors and derived PDTOs from an understudied NEN subtype, large cell neuroendocrine carcinoma (LCNEC). PDTOs maintain the gene expression patterns, intra-tumoral heterogeneity, and evolutionary processes of parental tumors. Through drug sensitivity analyses, we uncover therapeutic sensitivities to an inhibitor of NAD salvage biosynthesis and to an inhibitor of BCL-2. Finally, we identify a dependency on EGF in pulmonary neuroendocrine tumor PDTOs. Consistent with these findings, analysis of an independent cohort showed that approximately 50% of pulmonary neuroendocrine tumors expressed EGFR. This study identifies a potentially actionable vulnerability for a subset of NENs, and further highlights the utility of these novel PDTO models for the study of NENs.

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“…The epidermal growth factor receptor (EGFR) is a member of the ErbB family of receptor tyrosine kinases, and its dysregulation has been implicated in various cancers, including certain types of NETs [13,14] (Figure 4). The role of EGFR in NETs is complex, and its significance can vary among different subtypes of neuroendocrine tumors [15].…”

Section: Egfrmentioning

confidence: 99%

“…But mutations are not the sole genetic alterations affecting EGFR behavior in NETs. Marinović et al demonstrated an association between EGFR polymorphism +1562 AG and susceptibility to NET development [13]. In essence, genetic mutations or alterations affecting EGFR in NETs can significantly impact treatment strategies and tumor susceptibility.…”

Section: Egfrmentioning

confidence: 99%

Exploring Emerging Therapeutic Targets and Opportunities in Neuroendocrine Tumors: Updates on Receptor Tyrosine Kinases

Toffoli,

Ditsiou,

Gagliano

2024

Receptors

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Neuroendocrine tumors (NETs) represent a diverse group of neoplasms originating from neuroendocrine cells, presenting varied clinical behaviors and posing significant challenges in management. This review explores the emerging roles of receptor tyrosine kinases (RTKs) in the pathogenesis and progression of NETs, including vascular endothelial growth factor receptors (VEGFRs), insulin-like growth factor receptors (IGF-1R), RET, epidermal growth factor receptor (EGFR), and ALK. The dysregulation of RTK signaling pathways contributes to key cellular processes such as proliferation, survival, and invasion in NETs. We discuss the potential of targeting RTKs as therapeutic strategies in NETs, with a focus on recent developments in RET inhibitors and the therapeutic implications of RTK alterations.

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Analysis of polymorphisms in EGF, EGFR and HER2 genes in pancreatic neuroendocrine tumors (PNETs)

Cited by 5 publications

References 46 publications

Evolutionary Trajectories of Primary and Metastatic Pancreatic Neuroendocrine Tumors Based on Genomic Variations

Evolutionary Trajectories of Primary and Metastatic Pancreatic Neuroendocrine Tumors Based on Genomic Variations

Druggable Growth Dependencies and Tumor Evolution Analysis in Patient-Derived Organoids of Neuroendocrine Cancer

Exploring Emerging Therapeutic Targets and Opportunities in Neuroendocrine Tumors: Updates on Receptor Tyrosine Kinases

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