Diagnosing idh1 related subgroups and treatment of cancer
a cancer and related technology, applied in the field of medicine, can solve the problems of reducing the power of clinical trials, reducing the development of new therapies, and little improvement over the last 30 years, and achieve the effects of reducing the likelihood of having, slowing the progression of a cancer subtype, and reducing the severity of the diseas
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[0218]Patient Information
[0219]The discovery dataset (GBM195) consisted of 181 GBM (WHO grade IV astrocytoma; (159 primary and 22 recurrent) from 3 datasets [3], [4], [21] and 14 non-neoplastic samples from 2 sources: (1) six samples from patients undergoing temporal lobe epilepsy surgery [3] and (2) eight samples from autopsy specimens of cerebral cortex from donors with no history of neurological disorders obtained from the National Neurological Research Brain Bank (Los Angeles, Calif.) [4]. Two datasets are in GEO (GSE4271, GSE4412) and the third has been submitted. Table 1 lists GEO ID's and clinical information for GBM195 tumors. Tissue collection and processing, pathological review, and microarray analysis for the discovery dataset (GBM195) has been described elsewhere ([3] Nigro et al. 2005, [4] Phillips et a. 2006, and [21] Freije et al. 2004, which are incorporated herein by reference in their entirety as though fully set forth.) The validation dataset consisted ...
example 2
ay Genes Define 5 Prognostic Subgroups in Glioblastoma
[0233]AKT Pathway Gene Expression Divides GBM into at Least Six Subgroups
[0234]The inventors investigated AKT pathway variations in GBM by developing a list of AKT pathway genes (Table 2) then applying consensus clustering for the number of clusters k=2 to 10 (FIG. 9; FIG. 1A shows results for k=5 to 8). The inventors evaluated cluster stability using the consensus cumulative distribution function (CDF) plot of the consensus index (FIG. 1C) [25]. Cluster stability increased for k=2 to 6 but not appreciably for k>6 (FIG. 1C); suggesting six is the optimum number of GBM AKT subgroups. Silhouette width values were computed for each sample [26] (FIG. 1B) and samples with a positive silhouette width were selected for further analyses.
[0235]The inventors aim to have a classification system where clinical differences are maximized. Here, the inventors investigated how survival of patient subgroups varies with k. FIG. 1D plots the correc...
example 3
al Patients Benefit from Temozolomide
[0264]The AKT pathway can be a dominant determinant of response to diverse therapeutics including chemotherapy. The chemotherapy Temozolomide (TMZ; 6 cycles), is currently standard of care for newly diagnosed Glioblastoma. Here we show that AKT classification predicts response to TMZ in Glioblastoma.
[0265]We plotted Kaplan Meier survival curves for patients treated with more vs. less TMZ in each AKT subgroup (FIG. 17). Since most TCGA patients received some TMZ, it was not possible to plot survival curves for patients treated with and without the drug. Instead, we compared survival in 2 treatment arms, those receiving more (≥3) vs. less (<3) cycles.
[0266]We found that patients in the Secondary-Like subtype treated with more TMZ did worse than those receiving less. There was a tendency for patients who received more TMZ to not have received a nitrosourea. We showed evidence that CCNU / BCNU provides a 4.5 year survival advantage to Secondary-Like pa...
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