Dna markers for management of cancer

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.

1 - 31 . (canceled) 
     
     
         32 . A kit, comprising one or more agents for detecting LOH, DNA hypermethylation or gene mutation of one or more DNA markers in a bodily fluid or tissue sample. 
     
     
         33 . The kit of  claim 32 , wherein the bodily fluid or tissue sample is a cell-free bone marrow sample 
     
     
         34 . A packaged product, comprising
 a container;   one or more agents for detecting one or more DNA markers in a bodily fluid or tissue sample from a subject; and   an insert associated with the container, the insert comprising a label or instruction sheet indicating the diagnosis, stage, or prognosis of cancer in the subject based on the detection of the one or more agents.   
     
     
         35 . The packaged product of  claim 34 , wherein the bodily fluid or tissue sample is a cell-free bone marrow sample 
     
     
         36 . The packaged product of  claim 34 , wherein the DNA markers are indicative of LOH, DNA hypermethylation or DNA mutation, or a combination thereof. 
     
     
         37 . The packaged product of  claim 36 , wherein the DNA markers include one or more of the group consisting of D1S228, D8S321, D4S175, D4S1586, D5S299, D8S133, D8S261, D8S262, D8S264, D9S171, D10S197, D10S591, D10S532, D14S51, D14S62, D15S127, D16S421, D16S422, D17S796, D17S849, D17S855, D18S58, D18S61, and D18S70 
     
     
         38 . The packaged product of  claim 36 , wherein the DNA markers indicative of DNA hypermethylation include one or more of the group consisting of RASSF1A, MGMT, GSTP1, RAR-.beta., TWIST, APC, DAPK, P16, or Cyclin D2 promoter. 
     
     
         39 . The packaged product of  claim 36 , wherein the DNA markers indicative of DNA mutation include KRAS gene muration or BRAF gene mutation. 
     
     
         40 . The packaged product of  claim 34 , wherein the insert indicates that LOH, DNA hypermethylation or DNA mutation of the one or more DNA markers is indicative of a cancer diagnosis in the subject. 
     
     
         41 . The packaged product of  claim 34 , wherein the insert indicates that a combination of LOH, DNA hypermethylation or DNA mutation of the one or more DNA markers is indicative of a cancer diagnosis in the subject. 
     
     
         42 . The packaged product of  claim 34 , wherein the insert indicates that LOH, DNA hypermethylation or DNA mutation of the one or more DNA markers is indicative of an advanced stage of a cancer or a poor prognosis of a cancer in the subject. 
     
     
         43 . The packaged product of  claim 34 , wherein the insert indicates that a combination of LOH, DNA hypermethylation or DNA mutation of the one or more DNA markers is indicative of an advanced stage of a cancer or a poor prognosis of a cancer in the subject. 
     
     
         44 . A packaged product, comprising
 a container;   one or more agents for detecting LOH, DNA hypermethylation or gene mutation of one or more DNA markers in a cell-free bone marrow sample from a subject; and   an insert associated with the container, the insert comprising a label or instruction sheet indicating the diagnosis, stage, or prognosis of cancer in the subject based on the detection of LOH, DNA hypermethylation or gene mutation of the one or more DNA markers.   
     
     
         45 . The packaged product of  claim 44 , wherein the DNA markers include one or more of the group consisting of D1S228, D8S321, D4S175, D4S1586, D5S299, D8S133, D8S261, D8S262, D8S264, D9S171, D10S197, D10S591, D10S532, D14S51, D14S62, D15S127, D16S421, D16S422, D17S796, D17S849, D17S855, D18S58, D18S61, and D18S70 
     
     
         46 . The packaged product of  claim 44 , wherein the DNA markers indicative of DNA hypermethylation include one or more of the group consisting of RASSF1 A, MGMT, GSTP1, RAR-.beta., TWIST, APC, DAPK, P16, or Cyclin D2 promoter. 
     
     
         47 . The packaged product of  claim 44 , wherein the DNA markers indicative of DNA mutation include KRAS gene muration or BRAF gene mutation. 
     
     
         48 . The packaged product of  claim 44 , wherein the insert indicates that LOH, DNA hypermethylation or DNA mutation of the one or more DNA markers is indicative of a cancer diagnosis in the subject. 
     
     
         49 . The packaged product of  claim 44 , wherein the insert indicates that a combination of LOH, DNA hypermethylation or DNA mutation of the one or more DNA markers is indicative of a cancer diagnosis in the subject. 
     
     
         50 . The packaged product of  claim 44 , wherein the insert indicates that LOH, DNA hypermethylation or DNA mutation of the one or more DNA markers is indicative of an advanced stage of a cancer or a poor prognosis of a cancer in the subject. 
     
     
         51 . The packaged product of  claim 44 , wherein the insert indicates that a combination of LOH, DNA hypermethylation or DNA mutation of the one or more DNA markers is indicative of an advanced stage of a cancer or a poor prognosis of a cancer in the subject.