Metabolism, Gliomas, andIDH1

Abstract

Please be advised that this information was generated on 2020-08-05 and may be subject to change. clinical implications of basic researchT h e ne w e ngl a nd jou r na l o f m e dic i ne n engl j med 362;12 nejm.org march 25, 2010

Assessment of bevacizumab resistance increased by expression of BCAT1 in IDH1 wild-type glioblastoma: application of DSC perfusion MR imaging

“…GBM, the most aggressive subtype of glioma, has high vascularization and diverse genetic alterations [1, 25, 26]. Given the dismal prognosis of GBM, it would be advantageous to identify early biomarkers of a response to therapy to avoid continuing ineffective treatments and to initiate other therapeutic strategies [1, 27, 28].…”

EGFR, p53, IDH-1 and MDM2 immunohistochemical analysis in glioblastoma: therapeutic and prognostic correlation

“…This ratio is close to the number found in more recent studies 1,8 , which is around 5%. The mutation of IDH-1 seems to point to a slightly better prognosis and perhaps this is the reason to be found more frequently in secondary tumors 8,9,10 . However, in our sample of patients, we found only one case of secondary glioblastoma, which was negative for the mutated form of IDH-1.…”

“…of a secondary glioblastoma be positive for this mutation is less than 20% 1,8,9 . The immunostaining for Murine Double Protein 2 (MDM2) was nuclear with an irregular distribution throughout the section.…”

“…All of the IDH1 mutations known to date are heterozygous and somatic. The most common alteration in the protein occurs in the amino acid position 132 and determines the substitution of arginine for histidine (R132H) 8,9,10,11,12,13 . IDH1 mutations alter the normal enzyme activity reducing the synthesis of α-ketoglutarate and NADPH, which makes the cell more susceptible to oxidative stress.…”

IDH1 and IDH2 mutations in myeloid neoplasms - Novel paradigms and clinical implications

“…6 Since overproduction of this metabolite is associated with a high risk of brain tumors in patients with inborn metabolic errors, the authors concluded that the accumulation of excess 2-hydroxyglutarate in vivo contributes to the formation and malignant progression of gliomas, establishing a link between abnormal metabolism and malignancy. 7 The altered metabolic pathway associat-© F e r r a t a S t o r t i F o u n d a t i o n ed with mutant IDH1 has also been shown to contribute to tumor growth by activating hypoxia-inducible factor-1a. 8 These observations have important clinical implications, as patients with initial or low-grade forms of glioma may benefit from the therapeutic inhibition of 2-hydroxyglutarate production.…”