Genetic and Molecular Biomarkers in Aggressive Pheochromocytomas and Paragangliomas
Abstract
:1. Introduction
2. Genetic Aberrations in PPGLs
2.1. Cluster 1
2.2. Cluster 2
2.3. Cluster 3
2.4. Other Genes Involved in PPGL Oncogenesis
3. Molecular and Biochemical Markers
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Germline and Somatic Mutations | Exclusively Somatic Mutations | ||
---|---|---|---|
Cluster 1 (Pseudohypoxic cluster) | Cluster 1A | SDHx (A/B/C/D), SDHAF2, FH, MDH2, GOT2, DLST, SLC25A11 | IDH1/2 |
Cluster 1B | EGLN1/2, VHL | EPAS1 (HIF2α) | |
Cluster 2 (Kinase signaling cluster) | RET, MERTK, MET, NF1, MAX, TMEM127 | FGFR1, HRAS, BRAF | |
Cluster 3 (Wnt signaling cluster) | - | CSDE1, UBTF-MAML3 |
Gene | Function | Risk of Aggressive Behavior |
---|---|---|
VHL—von Hippel–Lindau | Regulates HIF degradation | Low (8%) |
SDHA—Succinate dehydrogenase subunit A | Subunit of mitochondrial protein complex SDH | High (30–66%) |
SDHB—Succinate dehydrogenase subunit B | Subunit of mitochondrial protein complex SDH | High (66–83%) |
SDHC—Succinate dehydrogenase subunit C | Subunit of mitochondrial protein complex SDH | Low |
SDHD—Succinate dehydrogenase subunit D | Subunit of mitochondrial protein complex SDH | Medium (15–29%) |
SDHAF2—Succinate dehydrogenase complex assembly factor 1 | Participates in assembly of mitochondrial protein complex SDH | Low |
FH—Fumarate hydratase | Catalyzes the conversion of fumarate to malate | High (60%) |
RET—Rearranged during transfection | Tyrosine kinase receptor | Low (<5%) |
NF1—Neurofibromin 1 | Inhibits RAS signaling pathway | Medium-High (12%) |
TMEM127—Transmembrane protein 127 | Inhibits mTOR signaling pathway | Low (<5%) |
MAX—MYC-associated factor X | Participates in cellular proliferation, differentiation, and apoptosis | Medium (10%) |
Tp53—Tumor suppressor protein 53 | Regulates cell cycle | High |
Syndrome | Gene, Chromosome Location | Metastatic Disease (%) | Recurrence (%) | Associated Tumors |
---|---|---|---|---|
PPGL1 | SDHD, 11q23.1 | 15–29 | 60 | Gastrointestinal stromal tumors, pituitary tumors |
PPGL2 | SDHAF2, 11q12.2 | - | unknown | |
PPGL3 | SDHC, 1q23.3 | 8–28 | unknown | Renal carcinoma, gastrointestinal stromal tumors |
PPGL4 | SDHB, 1p36.13 | 66–83 | unknown | Renal carcinoma, gastrointestinal stromal tumors, pituitary tumors |
PPGL5 | SDHA, 5p15.33 | 30–66 | unknown | Gastrointestinal stromal tumors, pituitary tumors |
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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Torresan, F.; Iacobone, C.; Giorgino, F.; Iacobone, M. Genetic and Molecular Biomarkers in Aggressive Pheochromocytomas and Paragangliomas. Int. J. Mol. Sci. 2024, 25, 7142. https://doi.org/10.3390/ijms25137142
Torresan F, Iacobone C, Giorgino F, Iacobone M. Genetic and Molecular Biomarkers in Aggressive Pheochromocytomas and Paragangliomas. International Journal of Molecular Sciences. 2024; 25(13):7142. https://doi.org/10.3390/ijms25137142
Chicago/Turabian StyleTorresan, Francesca, Clelia Iacobone, Francesco Giorgino, and Maurizio Iacobone. 2024. "Genetic and Molecular Biomarkers in Aggressive Pheochromocytomas and Paragangliomas" International Journal of Molecular Sciences 25, no. 13: 7142. https://doi.org/10.3390/ijms25137142