In application to the glioblastoma dataset from The Cancer Genome Atlas, MHN proposed a novel interaction in line with consecutive biopsies: IDH1 mutations are early events that promote subsequent fixation of TP53 mutations.
Drugs targeting wild-type <i>IDH1</i> may thus have clinical utility in GCs exhibiting <i>HNF4α</i> overexpression, expanding the role of <i>IDH1</i> in cancer beyond <i>IDH1/2</i> mutated malignancies.
Literature search revealed a virtual absence of IDH2 R172 and IDH1R132S mutations in >1000 cases of 8 different malignancies included in the differential diagnosis of sinonasal undifferentiated carcinoma.
This effect involves excessive anaplerosis, as demonstrated by the fact that inhibition of isocitrate dehydrogenase-1, IDH1, reduced the efficacy of cancer cell killing by the combination treatment.
Applied to study reductive glutamine metabolism in cancer cells, shown to mediate fatty acid biosynthesis under hypoxia and defective mitochondria, we find a previously unappreciated role of reductive IDH1 as the sole net contributor of carbons to fatty acid biosynthesis under standard normoxic conditions in HeLa cells.
Additionally, the potentially targetable IDH1 R132 mutation was present in 7% of IBD-CRCs but only 1% of sporadic CRCs and The Cancer Genome Atlas CRCs; alterations in other genes with potential targeted therapies were very rare.
Using longitudinal molecular profiling, Körber et al. propose in this issue of Cancer Cell that IDH-wild-type glioblastomas initiate years pre-diagnosis with chromosome-level alterations that drive cell proliferation but require survival-promoting mutations, commonly in the TERT promoter, to form a detectable tumor.
Using an integrated functional genomics approach, we prioritized networks associated with astrocytoma progression using the following criteria: differential co-expression between grade II and grade III IDH1-mutated and 1p/19q euploid astrocytomas, preferential enrichment for genetic risk to cancer, association with patient survival and sample-level genomic features.
In this review, we summarize current knowledge regarding the function of normal and mutated IDH, explain the possible mechanisms through which these mutations might drive malignant transformation of progenitor cells in the central nervous system, and provide a comprehensive review of potential treatment strategies for IDH-mutated malignancies, focusing on gliomas.
Cancer astrocytes have a more conserved molecular status in long recurrence free survival (RFS) IDH1 wild-type glioblastoma patients: new emerging cancer players.
A comparison with other molecular tumor features available from earlier studies revealed that TMPRSS2-ERG fusion as well as deletion of PTEN, 5q21, 6q15, and 3p13 was less frequent in IDH1-mutated than in non-mutated cancer.