Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-7718364-B2
Publication Date
2010-05-18
Expiration Date
Abstract
A method is provided for assessing allelic losses and hypermethylation of genes in CpG tumor promotor region on specific chromosomal regions in cancer patients, including melanoma, neuroblastoma breast, colorectal, and prostate cancer patients. The method relies on the evidence that free DNA and hypermethylation of genes in CpG tumor promotor region may be identified in the bone marrow, serum, plasma, and tumor tissue samples of cancer patients. Methods of melanoma, neuroblastoma, colorectal cancer, breast cancer and prostate cancer detection, staging, and prognosis are also provided.
Core Innovation
The invention relates to detecting DNA markers in a sample provided as a cell-free bone marrow sample from a subject. One or more DNA markers are detected in the sample, where the DNA markers are indicative of LOH or DNA hypermethylation, and the approach further includes detecting DNA mutation in KRAS or BRAF gene when the DNA markers include KRAS or BRAF.
The invention provides detection methods in which a combination of LOH and DNA hypermethylation is detected in the sample. LOH is indicated by one or more DNA markers, including specified marker loci, and DNA hypermethylation is detected in promoter regions of one or more named genes, including RASSF1A, MGMT, GSTP1, RAR-β, TWIST, APC, DAPK, or Cyclin D2.
The invention applies the detected DNA markers to cancer-related determinations in a subject. The presence of LOH, hypermethylation, or mutation of the markers is indicative of cancer, and a combination of LOH and hypermethylation is indicative of cancer. The markers are also used to indicate an advanced stage of cancer and to indicate a poor prognosis of the cancer.
Claims Coverage
The independent claims cover five core inventive features using cell-free bone marrow: detecting DNA markers indicative of LOH and/or DNA hypermethylation and/or KRAS/BRAF mutation; detecting a combined LOH plus DNA hypermethylation profile; using marker detection to detect cancer; and using marker detection to stage and prognose cancer as advanced stage and poor prognosis. The independent claims include five inventive-feature sets.
Detecting DNA markers in cell-free bone marrow
providing a cell-free bone marrow sample from a subject; and detecting one or more DNA markers in the sample, wherein the DNA markers are indicative of LOH or DNA hypermethylation, or the DNA markers are indicative of DNA mutation in KRAS or BRAF gene.
Detecting a combination of loh and DNA hypermethylation
providing a cell-free bone marrow sample from a subject; and detecting a combination of LOH and DNA hypermethylation in the sample.
Cancer detection using LOH and hypermethylation marker combinations
providing a cell-free bone marrow sample from a subject; and detecting one or more DNA markers in the sample, wherein a combination of LOH and hypermethylation of the markers is indicative of cancer in the subject.
Staging cancer with LOH, hypermethylation, or mutation
providing a cell-free bone marrow sample from a subject suffering from cancer; and detecting one or more DNA markers in the sample, wherein LOH, hypermethylation, or mutation of the markers is indicative of an advanced stage of the cancer in the subject.
Prognosing cancer with LOH, hypermethylation, or mutation
providing a cell-free bone marrow sample from a subject suffering from cancer; and detecting one or more DNA markers in the sample, wherein LOH, hypermethylation, or mutation of the markers is indicative of a poor prognosis of the cancer in the subject.
Across the independent claims, the coverage is centered on detecting one or more DNA markers in a cell-free bone marrow sample, with marker indications spanning LOH, DNA hypermethylation, and KRAS or BRAF mutation. Additional independent claim coverage specifically recites detecting a combination of LOH and DNA hypermethylation, and using the detected marker indications for cancer detection, staging as advanced stage, and prognosing as poor prognosis.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Detecting cancer in a subject based on LOH, hypermethylation, and/or KRAS/BRAF mutation indicators in detected DNA markers using a cell-free bone marrow sample.
Staging cancer by indicating an advanced stage of cancer in a subject using LOH, hypermethylation, or mutation of detected DNA markers in a cell-free bone marrow sample.
Prognosing cancer by indicating a poor prognosis of the cancer in a subject using LOH, hypermethylation, or mutation of detected DNA markers in a cell-free bone marrow sample.
Interested in licensing this patent?