Genetic alterations in glioma
Methods and genetic sequences are described for use in determining the diagnosis, subtype, prognosis, and disease course of high-grade gliomas, such as glioblastoma multiforme. One such method includes determining increased expression of at least one gene on a chromosome segment in cells of the glioma, the segment being 17:57,851,812-17:57,973,757; 7:127,892,509-7:127,947,649; 12:33,854-12:264,310; or 19:33,329,393-19:35,322,055; and estimating, based on the expression, a predicted length of survival, a probability of survival, or a predicted response to a therapy for the glioma.
1. A method of diagnosing and treating a glioma with increased responsiveness to temozolomide in a patient, the method comprising:
a) obtaining a sample comprising at least one cell of the glioma from the patient;
b) measuring the copy number of a genetic segment encompassing Tlk2 and Mettl2a in the at least one cell of the glioma from the patient and comparing the copy number of the genetic segment encompassing Tlk2 and Mettl2a to the copy number of the genetic segment encompassing Tlk2 and Mettl2a of a normal cell;
c) diagnosing the patient with glioma with increased responsiveness to temozolomide when the copy number of the genetic segment encompassing Tlk2 and Mettl2a from the at least one cell of the glioma from the patient is increased compared to the copy number of the genetic segment encompassing Tlk2 and Mettl2a from the normal cell; and
d) administering temozolomide to the patient diagnosed with increased responsiveness to temozolomide.
2. The method of claim 1 , wherein the patient has further been identified as having an increased copy number of at least one other nucleotide sequence from the at least one cell of the glioma from the patient, the at least one other nucleotide sequence having at least 90 percent sequence identity to at least one of, respectively, SEQ ID NO:7 or 8; SEQ ID NO:9 or 10; SEQ ID NO:11; SEQ ID NO:12, 13, 14, 15,16, 17, or 18; SEQ ID NO: 19, 20, or 21; SEQ ID NO: 22, 23, or 24; SEQ ID NO: 25, 26, or 27; SEQ ID NO: 28; SEQ ID NO: 29, 30, or 31; SEQ ID NO: 32 or 33; SEQ ID NO: 34, 35, 36, or 37; SEQ ID NO: 38; SEQ ID NO: 39; SEQ ID NO: 40; SEQ ID NO: 41; SEQ ID NO: 42; SEQ ID NO: 43; or SEQ ID NO: 44-45.
3. The method of claim 1 , wherein the glioma comprises an astrocytoma.
4. The method of claim 1 , wherein the glioma comprises a glioblastoma multiforme.
5. The method of claim 1 , wherein the increased copy number was determined by a technique selected from the group consisting of: fluorescent in-situ hybridization, complementary genomic hybridization, array complementary genomic hybridization, fluorescence microscopy, oligonucleotide genotyping, sequencing, southern blotting, dynamic allele-specific hybridization (DASH), paralogue ratio rest (PRT), multiple amplicon quantification (MAO), quantitative polymerase chain reaction (QPCR), multiplex ligation dependent probe amplification (MLPA), multiplex amplification and probe hybridization (MAPH), quantitative multiplex PCR of short fluorescent fragment (QMPSF), dynamic allele-specific hybridization, fluorescence in situ hybridization (FISH), semiquantitative fluorescence in situ hybridization (SQ-FISH), and any combination thereof.
6. The method of claim 1 , wherein the administering is further based on at least one of the patient's age, sex or ethnicity.