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Published on: August 25, 2021
Activating FGFR1 Mutations in Sporadic Pheochromocytomas
Jenny Welander1, Małgorzata Łysiak1, Michael Brauckhoff2,3
1Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, 58185, Linköping, Sweden.
Researchers identified FGFR1 mutations in sporadic pheochromocytomas, a rare neuroendocrine tumor. This discovery advances understanding of tumor development and suggests FGFR1 activation is key in some cases.
Area of Science:
- Endocrinology and Oncology
- Genetics of Neuroendocrine Tumors
Background:
- Pheochromocytomas are adrenal neuroendocrine tumors with high heritability due to germline mutations.
- Sporadic pheochromocytomas often lack a clear genetic cause, despite somatic alterations in genes like NF1.
Purpose of the Study:
- To investigate the genomic landscape of sporadic pheochromocytomas.
- To identify novel genetic alterations contributing to sporadic pheochromocytoma development.
Main Methods:
- Whole-exome sequencing of 16 paired tumor and normal DNA samples.
- Confirmation analysis in two additional cohorts (total 80 sporadic pheochromocytomas).
- Gene expression microarray profiling.
Main Results:
- Identified an average of 33 non-silent somatic variants per tumor.
- Discovered activating FGFR1 mutations in 3.8% of sporadic pheochromocytomas.
- FGFR1-mutated tumors showed activation of MAPK and PI3K-AKT pathways, similar to NF1, RET, and HRAS-mutated tumors.
Conclusions:
- FGFR1 is the third proto-oncogene recurrently mutated in pheochromocytomas, alongside RET and HRAS.
- Somatic FGFR1 activation is a significant event in a subset of sporadic pheochromocytomas.
- Findings enhance the biological understanding of pheochromocytoma pathogenesis.
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