Compositions and methods for glioma classification
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.