Genetic Brain Tumor Markers
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Abstract
The invention relates to method of genetic analysis for the prediction of treatment sensitivity and survival prognosis of patients with brain tumors, especially oligodendroglial tumors. The invention provides a method for producing a classification scheme for oligodendroglial tumors comprising the steps of a) providing a plurality of reference samples, said reference samples comprising cell samples from a plurality of reference subjects suffering from oligodendroglial tumors; b) providing reference profiles by establishing a gene expression profile for each of said reference samples individually; c) clustering said individual reference profiles according to similarity; and d) assigning an oligodendroglial tumor class to each cluster.
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Citations
41 Claims
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1-21. -21. (canceled)
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22. A method for producing a classification scheme for oligodendroglial tumors comprising the steps of:
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a) providing a plurality of reference samples, said reference samples comprising cell samples from a plurality of reference subjects suffering from oligodendroglial tumors, with known responsiveness to therapy and survival or with known loss of heterozygosity of 1p or 19q; b) providing reference profiles by establishing a gene expression profile, matched with parameters for treatment sensitivity, survival and loss of heterozygosity for each of said reference samples individually; c) clustering said individual reference profiles according to a statistical procedure, comprising; (i) K-means clustering, (ii) hierarchical clustering, and (iii) Pearson correlation coefficient analysis; and d) assigning an oligodendroglial tumor class according to treatment sensitivity, survival or loss of heterozygosity to each cluster. - View Dependent Claims (23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)
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36. A method of determining the prognosis for a subject suffering from an oligodendroglial tumor, said method comprising the steps of:
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a) isolating an RNA from tumor cells of said subject; b) preparing an antisense, biotinylated RNA to said RNA of step a); c) hybridizing said antisense to said RNA; d) normalizing a plurality of measured values for a gene set of Table 3; e) clustering the obtained data together with the reference data, obtained from a reference set of patient with known prognosis; and f) determining the prognosis on basis of the cluster to which the data of the subject are clustering.
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- 37. An oligonucleotide microarray of maximal 500 probesets, comprising at least 1 oligonucleotide probe capable of hybridizing under stringent conditions to a gene of an oligodendroglial tumor-associated genes selected from Tables 3-7.
Specification