Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Gene/Protein
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Target Concepts:
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Disease
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Enzyme
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Query: EC:1.3.5.1 (
succinate dehydrogenase
)
8,177
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Approximately 85-90% of adult gastrointestinal stromal tumors (GISTs) harbor KIT and PDGFRA mutations. The remaining cases, including the majority of pediatric GISTs, lack these mutations, and have been designated as KIT/PDGFRA wild-type (WT) GISTs. Nearly 15% of WT GISTs harbor BRAF mutations, while others arise in patients with type I
neurofibromatosis
. Recent work has confirmed that 20-40% of KIT/PDGFRA WT GISTs show loss of function of
succinate dehydrogenase
complex. Less than 5% of GISTs lack known molecular alterations ("quadruple-negative" GISTs). Thus, it is important to consider genotyping these tumors to help better define their clinical behavior and therapy.
...
PMID:Genetics of Gastrointestinal Stromal Tumors: A Heterogeneous Family of Tumors? 2629 68
Gastrointestinal stromal tumor (GIST) is a mesenchymal tumor of the gastrointestinal tract. Mutation of KIT and PDGFRA genes is implicated in the tumorigenesis. Approximately 10% of GISTs do not harbor mutation of these genes, and they are designated as "wild type" GIST. They are classified into
succinate dehydrogenase
(
SDH
)-deficient and non-
SDH
-deficient groups.
SDH
-deficient group includes Carney triad and Carney Stratakis syndrome. The patients are young women. Tumors occur in the antrum of the stomach, and tumor cells are epithelioid. Lymph node metastasis is frequent. The non-
SDH
-deficient group includes
neurofibromatosis
(NF) type 1 and GISTs with mutations of BRAF, KRAS, and PIK3CA and with the ETV6-NTRK3 fusion gene. GIST in NF occurs in the small intestine, and tumor cells are spindle shaped. GIST with BRAF mutation arises in the small intestine. Attention to the age, gender, family history and other neoplasms may raise the prediction of syndromic disease. Location of the tumor, morphology, and pleomorphism of the tumor cells are further informative. Lymphovascular invasion should be carefully evaluated. The determination of KIT expression is essential for the diagnosis. When wild type GIST is suspected, intensive genetic analysis is required. Further, a careful and long-time observation is recommended.
...
PMID:"Wild type" GIST: Clinicopathological features and clinical practice. 2742 38
Static single-time-frame
18
F-FDG PET/CT is useful for the localization and functional characterization of pheochromocytomas and paragangliomas (PPGLs).
18
F-FDG uptake varies between PPGLs with different genotypes, and the highest SUVs are observed in cases of
succinate dehydrogenase
(
SDH
) mutations, possibly related to enhanced aerobic glycolysis in tumor cells. The exact determinants of
18
F-FDG accumulation in PPGLs are unknown. We performed dynamic PET/CT scanning to assess whether in vivo
18
F-FDG pharmacokinetics has added value over static PET to distinguish different genotypes.
Methods:
Dynamic
18
F-FDG PET/CT was performed on 13 sporadic PPGLs and 13 PPGLs from 11 patients with mutations in
SDH
complex subunits B and D, von Hippel-Lindau (
VHL
),
RET,
and
neurofibromin 1
(
NF1
). Pharmacokinetic analysis was performed using a 2-tissue-compartment tracer kinetic model. The derived transfer rate-constants for transmembranous glucose flux (
K
1
[in],
k
2
[out]) and intracellular phosphorylation (
k
3
), along with the vascular blood fraction (V
b
), were analyzed using nonlinear regression analysis. Glucose metabolic rate (MR
glc
) was calculated using Patlak linear regression analysis. The SUV
max
of the lesions was determined on additional static PET/CT images.
Results:
Both MR
glc
and SUV
max
were significantly higher for hereditary cluster 1 (
SDHx, VHL
) tumors than for hereditary cluster 2 (
RET, NF1
) and sporadic tumors (
P
< 0.01 and
P
< 0.05, respectively). Median
k
3
was significantly higher for cluster 1 than for sporadic tumors (
P
< 0.01). Median V
b
was significantly higher for cluster 1 than for cluster 2 tumors (
P
< 0.01). No statistically significant differences in
K
1
and
k
2
were found between the groups. Cutoffs for
k
3
to distinguish between cluster 1 and other tumors were established at 0.015 min
-1
(100% sensitivity, 15.8% specificity) and 0.636 min
-1
(100% specificity, 85.7% sensitivity). MR
glc
significantly correlated with SUV
max
(
P
= 0.001) and
k
3
(
P
= 0.002).
Conclusion:
In vivo metabolic tumor profiling in patients with PPGL can be achieved by assessing
18
F-FDG pharmacokinetics using dynamic PET/CT scanning. Cluster 1 PPGLs can be reliably identified by a high
18
F-FDG phosphorylation rate.
...
PMID:Metabolic Subtyping of Pheochromocytoma and Paraganglioma by
18
F-FDG Pharmacokinetics Using Dynamic PET/CT Scanning. 3041 58
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