Table Info

Table 2.

Various genes implicated in the PPGL pathogenesis, their impact on the tumorigenesis and the functional imaging specific to the cluster types

Cluster type	Sub-type	Germline or somatic	Exclusively somatic	Location of gene	Normal function	Impact of mutations	Nuclear imaging
Pseudohypoxia	Cluster 1A	SDHA SDHB SDHC SDHD SDHAF2 FH MDH2 IDH3B GOT2 DLST SLC25A11 SUCLG2	IDH1 IDH2	5p15 1p36.1-p35 1q23.3 11q23.1 11q12.2 1q42.1 7q11.23 20p13 16q21 14q24.3 17p13.2 3p14.1 2q34 15q26.1	Regulate oxygen levels and HIF activity	HIF accumulation, propelling angiogenesis, and tumor expansion	⁶⁸Ga-DOTATATE positron emission tomography/computed tomography (PET/CT)
Pseudohypoxia	Cluster 1B	VHL EGLN1 EGLN2	EPAS1	3p25.3 1q42.2 19q13.2 2p21	Regulate oxygen levels and HIF activity	HIF accumulation, propelling angiogenesis, and tumor expansion	¹⁸F-FDOPA imaging
Kinase signaling	Cluster 2A and 2B	NF1 RET MAX TMEM127 MET MERTK	FGFR1 HRAS BRAF	17q11.2 10q11.21 14q23.3 2q11.2 7q31 2q14.1 8p11.23 11p15.5 7q34	Control cell growth and proliferation	Cell proliferation, differentiation, and apoptosis	¹⁸F-FDOPA imaging
Wnt signaling	None	None	CSDE1 UBTF-MAML3	1p13.3 4q31.3	Regulate cellular differentiation and proliferation	Anomalous cell differentiation and tumorigenesis	None

GOT2: glutamic-oxaloacetic transaminase 2; DLST: dihydrolipoamide succinyltransferase; SLC25A11: solute carrier family 25 member 11; SUCLG2: succinate-CoA ligase GDP-forming subunit beta 2; MET: mesenchymal-epithelial transition factor; MERTK: myeloid-epithelial-reproductive tyrosine kinase; FGFR1: fibroblast growth factor receptor 1; HRAS: Harvey rat sarcoma viral oncogene homolog; BRAF: B-type Raf kinase; UBTF: upstream binding transcription factor; ⁶⁸Ga-DOTA-TATE: ⁶⁸Gallium-DOTA-Tyr3-octreotate; ¹⁸F-FDOPA: 6-L-¹⁸F-fluorodihydroxyphenylalanine

Declarations

Author contributions

MSJ and NM: Resources, Writing—original draft, Writing—review & editing. CFJ and JMP: Conceptualization, Supervision, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

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