Biomarkers For Head And Neck Cancer And Methods Of Their Use
AssigneeThe Regents of the University of Colorado, a body corporate
InventorsShi-long LU, John SONG
Life of this patent
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Abstract
Disclosed is a diagnostic panel of methylated genomic loci encoding microRNA (mgmiR) markers that demonstrated 90% sensitivity and 100% specificity in the detection of head and neck squamous cell carcinoma (HNSCC). These results represent the first use of quantitative MS-PCR for the detection of mgmiRs. In addition this panel demonstrates the ability to detect hypermethylation in the adjacent mucosa of cancer patients, suggesting its utility in early detection. This panel is also capable of detecting cancer by using saliva, blood and FNA tissue samples.
Claims25
A method for detecting cancer in a subject, comprising
- (a) measuring methylation level of at least one genomic locus encoding at least one microRNA (mgmiR) in a tissue or body fluid isolated from said subject, said at least one mgmiR being selected from the group consisting of 124-1, 124-2, 124-3, 137, and 9-1, and
- (b) comparing the methylation level of said at least one genomic locus encoding at least one microRNA (mgmiR) with a base methylation level, said base methylation level being the methylation level of the same mgmiR from the same tissue or body fluid of an individual known to be free from said cancer,
- wherein a significantly higher methylation level of said at least one mgmiR in the subject as compared to the base methylation level is indicative of cancer or pre-cancer in said subject.
A method for detecting cancer in a subject, comprising
- (a) measuring level of at least one microRNA in a tissue or body fluid isolated from said subject, said at least one microRNA being selected from the group consisting of 124-1, 124-2, 124-3, 137, and 9-1, and
- (b) comparing the level of said at least one microRNA with a base microRNA level, said base microRNA level being the level of the same microRNA from the same tissue or body fluid of an individual known to be free from said cancer, wherein a significantly lower level of said at least one microRNA in the subject as compared to the base microRNA level is indicative of cancer or pre-cancer.
A method for detecting cancer in a subject, comprising
- (a) preparing a DNA extract from a tissue or a body fluid of said subject, said DNA extract comprising a first DNA fragment encompassing at least one genomic locus encoding at least one microRNA selected from the group consisting of 124-1, 124-2, 124-3, 137, and 9-1,
- (b) generating a second DNA fragment by quantitative polymerase chain reaction (qPCR) using as a template said first DNA fragment and using as primers oligonucleotides specific to methylated DNA,
- (c) measuring the level of said second DNA fragment generated in step (b), and
- (d) comparing the level of said second DNA fragment with a base level, said base level being the level of a corresponding DNA fragment generated by the same manner from the same tissue or body fluid of an individual known to be free from said cancer,
- wherein a higher level of said second DNA fragment as compared to said base level is indicative of cancer or pre-cancer.
A method for treating head and neck squamous cell carcinoma (HNSCC) in a subject, comprising
- (a) removing a cancerous tissue comprising head and neck squamous cell carcinoma from a HNSCC cancer site of said subject,
- (b) isolating a plurality of cells adjacent to said cancer site,
- (c) measuring the level of at least one microRNA in said plurality of cells, said at least one microRNA being selected from the group consisting of 124-1, 124-2, 124-3, 137 and 9-1,
- (d) comparing the level of said at least one microRNA from step (c) with a base microRNA level, said base microRNA level being the level of the same microRNA in a non-cancerous tissue or body fluid from an individual known to be free from said cancer, and
- (e) repeat steps (a)-(d) until the level of said at least one microRNA in the plurality of cells is at least 90% of the base microRNA level.
A method for detecting HPV in a subject, comprising
- (a) measuring methylation level of at least one genomic locus encoding at least one microRNA (mgmiR) in a tissue or body fluid isolated from said subject, said at least one mgmiR being selected from the group consisting of 124-1, 124-2, 124-3, 137, and 9-1, and
- (b) comparing the methylation level of said at least one genomic locus encoding at least one microRNA (mgmiR) with a base methylation level, said base methylation level being the methylation level of the same mgmiR from the same tissue or body fluid of an individual known to be free from HPV,
- wherein a significantly higher methylation level of said at least one mgmiR in the subject as compared to the base methylation level is indicative of HPV infection in said subject.
A composition comprising an oligonucleotide selected from the group consisting of SEQ ID Nos.1-10.
Dependencies are inferred from the claim text.