Compositions and methods for glioma classification

Abstract

The present invention provides novel compositions and their use in classifying gliomas. In a preferred embodiment, the methods are used to discriminate between oligodendroglioma and glioblastoma.

1 . A composition comprising a glioma biomarker consisting of between 2 and 47 different probe sets, wherein at least 40% of the different probe sets comprise one or more isolated polynucleotides that selectively hybridize to a genomic region selected from the group consisting of 2q31.2; 4q23; 7q22.3; 9q31.2; 9p21-p13; 9q34.3; 10q26.13; 12q13.2; 14q13.2; 15q24.1; 15q22.2; 16q13.13; 16q22.1; 16q22.2; 16q24.1; 16q24.2; 16p12.2; 16p12.3; and 21q22.13; wherein the different probe sets in total selectively hybridize to at least two of the recited genomic regions. 
     
     
         2 . The composition of  claim 1  wherein the glioma biomarker consists of between 3 and 47 different probe sets, and wherein the different probe sets in total selectively hybridize to at least three of the recited genomic regions. 
     
     
         3 . The composition of  claim 1  wherein the glioma biomarker consists of between 4 and 47 different probe sets, and wherein the different probe sets in total selectively hybridize to at least four of the recited genomic regions. 
     
     
         4 . The composition of  claim 1  wherein the glioma biomarker consists of between 5 and 47 different probe sets, and wherein the different probe sets in total selectively hybridize to at least five of the recited genomic regions. 
     
     
         5 . A composition comprising a glioma biomarker consisting of between 2 and 47 different probe sets, wherein at least 40% of the different probe sets comprise one or more isolated polynucleotide sequences that selectively hybridize to a nucleic acid sequence according to formula 1, or its complement:
   X1-X2-X3   wherein X2 is selected from the group consisting SEQ ID NO: 19, SEQ ID NO:21 to 47, and SEQ ID NO:49-57; and   wherein X1 and X3 are independently 0-500 kB of human genomic nucleic acid sequences flanking X2 in the human genome; and   wherein the different polynucleotide probe sets in total selectively hybridize to at least two non-overlapping genomic sequences according to formula 1.   
     
     
         6 . The composition of  claim 5  wherein the glioma biomarker consists of between 3 and 47 different probe sets, and wherein the different polynucleotide probe sets in total selectively hybridize to at least three non-overlapping genomic sequences according to formula 1. 
     
     
         7 . The composition of  claim 5  wherein the glioma biomarker consists of between 4 and 47 different probe sets, and wherein the different polynucleotide probe sets in total selectively hybridize to at least four non-overlapping genomic sequences according to formula 1. 
     
     
         8 . The composition of  claim 5  wherein the glioma biomarker consists of between 5 and 47 different probe sets, and wherein the different polynucleotide probe sets in total selectively hybridize to at least five non-overlapping genomic sequences according to formula 1. 
     
     
         9 . The composition of  claim 5  wherein at least 40% of the different probe sets comprise one or more isolated polynucleotides of at least 10 nucleotides of a sequence according to formula 1, or its complement. 
     
     
         10 . The composition of  claim 9  wherein X1 and X3 are both 0. 
     
     
         11 . The composition of  claim 1  wherein the polynucleotides further comprise a detectable label. 
     
     
         12 . The composition of  claim 5  wherein the polynucleotides further comprise a detectable label. 
     
     
         13 . A composition comprising a glioma biomarker consisting of between 2 and 47 different probe sets, wherein at least 40% of the different probe sets comprise one or more isolated polynucleotides that selectively hybridize to a nucleic acid sequence according to SEQ ID NOS:1-13 and 15-20 or their complements; wherein the different probe sets in total selectively hybridize to at least two nucleic acid sequences according to SEQ ID NOS:1-13 and 15-20, or their complements. 
     
     
         14 . The composition of  claim 13  wherein the glioma biomarker consists of between 3 and 47 different probe sets, and wherein the different probe sets in total selectively hybridize to at least three of the recited nucleic acid sequences according to SEQ ID NOS:1-13 and 15-20, or their complements. 
     
     
         15 . The nucleic acid composition of  claim 13  wherein the glioma biomarker consists of between 4 and 47 different probe sets, and wherein the different probe sets in total selectively hybridize to at least four of the recited nucleic acid sequences according to SEQ ID NOS:1-13 and 15-20, or their complements. 
     
     
         16 . The nucleic acid composition of  claim 13  wherein the glioma biomarker consists of between 5 and 47 different probe sets, and wherein the different probe sets in total selectively hybridize to at least five of the recited nucleic acid sequences according to SEQ ID NOS:1-13 and 15-20, or their complements. 
     
     
         17 . The composition of  claim 13  wherein the polynucleotides further comprise a detectable label. 
     
     
         18 . A method for classifying a glioma, comprising
 (a) contacting a nucleic acid sample obtained from a subject having a glioma with a composition according to  claim 11  that, in total, selectively hybridize to two or more genomic regions selected from the group consisting of 2q31.2; 4q23; 7q22.3; 9q31.2; 9p21-p13; 9q34.3; 10q26.13; 12q13.2; 14q13.2; 15q24.1; 15q22.2; 16q13.13; 16q22.1; 16q22.2; 16q24.1; 16q24.2; 16p12.2; 16p12.3; and 21q22.13; wherein the contacting occurs under conditions to promote selective hybridization of the one or more nucleic acid probes to the two or more genomic regions;   (b) detecting formation of hybridization complexes;   (c) determining whether one or more of the genomic regions are present in an altered copy number in the nucleic acid sample; and   (d) correlating a decreased copy number of one or more of the genomic regions with a classification of the glioma as an oligodendroglioma, and correlating an absence of decreased copy number for one or more of the genomic regions with a classification of the glioma as a glioblastoma.   
     
     
         19 . A method for classifying a glioma, comprising
 (a) contacting a nucleic acid sample obtained from a subject having a glioma with a composition according to  claim 17  that, in total, selectively hybridize to at least two nucleic acid sequences according to SEQ ID NOS:1-13 and 15-20, or their complements, wherein the contacting occurs under conditions to promote selective hybridization of the composition to a genomic sequence according to formula 1 in the nucleic acid sample;   (b) detecting formation of hybridization complexes;   (c) determining whether one or more of the genomic sequences according to formula 1 are present in an altered copy number in the nucleic acid sample; and   (d) correlating a decreased copy number of one or more of the genomic sequences according to formula 1 with a classification of the glioma as an oligodendroglioma, and correlating an absence of decreased copy number for one or more of the genomic sequences according to formula 1 with a classification of the glioma as a glioblastoma.   
     
     
         20 . A method for treating a patient with a glioma, comprising,
 (a) classifying the glioma according to  claim 18 ; and   (b) determining a course of treatment for the patient based on the glioma classification.   
     
     
         21 . A method for treating a patient with a glioma, comprising,
 (a) classifying the glioma according to  claim 19 ; and   (b) determining a course of treatment for the patient based on the glioma classification.