Use of simultaneous marker detection for assessing diffuse glioma and responsiveness to treatment
AssigneeBioVentures, LLC
InventorsAnaliz Rodriguez, Thidathip Wongsurawat
Life of this patent
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Abstract
The present disclosure relates to a method to detect simultaneously mutations and methylation levels in a biological sample of a subject. In particular the present disclosure is directed to a method for diagnosing a central nervous system tumor such as a diffuse glioma, in a subject and comprises the steps of—determining at the same time the presence or absence of a mutation and methylation levels in one or more regions of interest.
Claims22
A method of treating a diffuse glioma in a human subject in need thereof, the method comprising:
- a) obtaining or having obtained a biological sample from the human subject;
- b) isolating genomic DNA from the sample;
- c) detecting or having detected simultaneously the mutational status of IDH1 or IDH2 genes and methylation levels in MGMT gene, including 5′ and 3′ flanking regions of the genes;
- wherein:
- (i) the mutational status of IDH1 comprises a substitution at R132;
- (ii) the mutational status of IDH2 comprises a substitution at R172;
- and
- (iii) the methylation levels in the MGMT gene comprises methylation levels in at least a portion of exon 1 and intron 1 of the MGMT gene;
- d) comparing the mutational status and the methylation levels of the genes with a reference value;
- e) indicating the human subject as having a diffuse glioma when the mutational status and the methylation levels of the genes deviate from the reference value;
- and
- f) administering to the human subject identified as having diffuse glioma, a treatment comprising chemotherapy or radiation.
A method of treating a human subject having a diffuse glioma, the method comprising:
- a) obtaining or having obtained a biological sample from the human subject;
- b) isolating genomic DNA from the sample;
- c) detecting or having detected methylation levels in MGMT gene, including 5′ and 3′ flanking regions of the gene;
- wherein:
- the methylation levels in the MGMT gene comprises methylation levels in at least a portion of exon 1 and intron 1 of the MGMT gene;
- d) comparing the methylation levels with a reference value;
- e) assessing therapy responsiveness in the human subject based on the methylation level of the MGMT gene;
- wherein, an increase in methylation levels in at least a portion of the exon 1 of the MGMT gene;
- or a decrease in the methylation level in at least a portion of intron 1 of the MGMT gene indicates that the subject has a diffuse glioma that is likely to respond to a chemotherapy comprising temozolomide;
- and
- f) administering temozolomide to the human subject indicated as likely to respond to chemotherapy comprising temozolomide.
A method of treating a diffuse glioma in a human subject in need thereof, comprising:
- administering to the human subject a treatment comprising chemotherapy or radiation, wherein the human subject has been determined as having the diffuse glioma when mutational status of IDH1 gene or IDH2 gene and methylation levels in MGMT gene, deviate from a reference value, in a sample obtained from the human subject;
- and wherein,
- (a) the mutational status of IDH1 comprises a substitution at R132;
- (b) the mutational status of IDH2 comprises a substitution at R172;
- and
- (c) the methylation levels in the MGMT gene comprises methylation levels in at least a portion of exon 1 and intron 1 of the MGMT gene.
A method of treating a diffuse glioma in a human subject in need thereof, comprising:
- administering to the human subject a treatment, wherein the human subject has been assessed as having a diffuse glioma that is likely to respond to a chemotherapy comprising temozolomide by having determined methylation levels in MGMT gene, including 5′ and 3′ flanking regions of the gene in a sample obtained from the human subject;
- wherein:
- determining the methylation levels in the MGMT gene comprises determining methylation levels in at least a portion of exon 1 and intron 1 of the MGMT gene;
- and
- wherein an increase in methylation levels in at least a portion the exon 1;
- or a decrease in the methylation level in at least a portion of the intron 1;
- indicates that the human subject is likely to respond to chemotherapy comprising temozolomide.
Dependencies are inferred from the claim text.