ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2012
Pancreatic endocrine tumours: mutational and immunohistochemical survey of protein kinases reveals alterations in targetable kinases in cancer cell lines and rare primaries.
Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 65 citations in OpenAlex.
- The Evolving Landscape of GEP-NENs in the Era of Precision Oncology: Molecular Insights into Tumor Heterogeneity.Cancers · 2025Review
- Neuroendocrine neoplasms of the pancreas: diagnosis and pitfalls.Virchows Archiv : an international journal of pathology · 2022Review
- Molecular biology of pancreatic neuroendocrine tumors: From mechanism to translation.Frontiers in oncology · 2022Review
- Pertuzumab Cardiotoxicity in Patients With HER2-Positive Cancer: A Systematic Review and Meta-analysis.CJC open · 2021Review
- Pancreatic neuroendocrine tumors G3 and pancreatic neuroendocrine carcinomas: Differences in basic biology and treatment.World journal of gastrointestinal oncology · 2020Review
- Molecular Signatures and Their Clinical Utility in Pancreatic Neuroendocrine Tumors.Frontiers in endocrinology · 2020Review
- Genetics and Epigenetics of Gastroenteropancreatic Neuroendocrine Neoplasms.Endocrine reviews · 2019Review
- Phospho-Protein Arrays as Effective Tools for Screening Possible Targets for Kinase Inhibitors and Their Use in Precision Pediatric Oncology.Frontiers in oncology · 2019Article
- Genetic alterations analysis in prognostic stratified groups identified TP53 and ARID1A as poor clinical performance markers in intrahepatic cholangiocarcinoma.Scientific reports · 2018Article
- Prognostic and predictive role of the PI3K-AKT-mTOR pathway in neuroendocrine neoplasms.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2018Review
- Reg3g Promotes Pancreatic Carcinogenesis in a Murine Model of Chronic Pancreatitis.Digestive diseases and sciences · 2015Article
- Tumor-associated macrophages are a useful biomarker to predict recurrence after surgical resection of nonfunctional pancreatic neuroendocrine tumors.Annals of surgery · 2014Article
- Multigene mutational profiling of cholangiocarcinomas identifies actionable molecular subgroups.Oncotarget · 2014Article
- Novel molecular targets for the treatment of gastroenteropancreatic endocrine tumors: answers and unsolved problems.International journal of molecular sciences · 2012Review
- Prognostic significance of ATM and cyclin B1 in pancreatic neuroendocrine tumor.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2012Article
- Profiling mTOR pathway in neuroendocrine tumors.Targeted oncology · 2012Review
- Ack1 tyrosine kinase activation correlates with pancreatic cancer progression.The American journal of pathology · 2012Article
- High KIT and PDGFRA are associated with shorter patients survival in gastroenteropancreatic neuroendocrine tumors, but mutations are a rare event.Journal of cancer research and clinical oncology · 2012Article
- Cell cycle control in acute myeloid leukemia.American journal of cancer research · 2012Article
- Genome-wide characterization of pancreatic adenocarcinoma patients using next generation sequencing.PloS one · 2012Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundKinases represent potential therapeutic targets in pancreatic endocrine tumours (PETs). PATIENTS AND
methodsThirty-five kinase genes were sequenced in 36 primary PETs and three PET cell lines: (i) 4 receptor tyrosine kinases (RTK), epithelial growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), tyrosine-protein kinase KIT (KIT), platelet-derived growth factor receptor alpha (PDGFRalpha); (ii) 6 belonging to the Akt/mTOR pathway; and (iii) 25 frequently mutated in cancers. The immunohistochemical expression of the four RTKs and the copy number of EGFR and HER2 were assessed in 140 PETs.
resultsSomatic mutations were found in KIT in one and ATM in two primary neoplasms. Among 140 PETs, EGFR was immunopositive in 18 (13%), HER2 in 3 (2%), KIT in 16 (11%), and PDGFRalpha in 135 (96%). HER2 amplification was found in 2/130 (1.5%) PETs. KIT membrane immunostaining was significantly associated with tumour aggressiveness and shorter patient survival. PET cell lines QGP1, CM and BON harboured mutations in FGFR3, FLT1/VEGFR1 and PIK3CA, respectively.
conclusionsOnly rare PET cases, harbouring either HER2 amplification or KIT mutation, might benefit from targeted drugs. KIT membrane expression deserves further attention as a prognostic marker. ATM mutation is involved in a proportion of PET. The finding of specific mutations in PET cell lines renders these models useful for preclinical studies involving pathway-specific therapies.
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