Diagnosing and Monitoring CNS Malignancies Using MicroRNA

Abstract

The use of specific microRNAs (miRNAs) present in CSF as biomarkers for particular brain malignancies and disease activity.

1 .- 8 . (canceled) 
     
     
         9 . A method of monitoring progression of a brain tumor, the method comprising: determining, using real time polymerase chain reaction (RT-PCR) or an RNA expression assay, levels of one or more of miR-10b, miR-21, and a miR-200 family member in a first sample comprising cerebrospinal fluid from a subject; and
 determining, using real time polymerase chain reaction (RT-PCR) or an RNA expression assay, levels of one or more of miR-10b, miR-21, and a miR-200 family member in a subsequent sample comprising cerebrospinal fluid from the subject;   comparing the levels of the one or more of miR-10b, miR-21, and a miR-200 family member in the first sample to the levels of the one or more of miR-10b, miR-21, and a miR-200 family member in the subsequent sample; and   determining presence of progression or recurrence of the brain tumor based on the presence of levels of miR-10b, miR-21, or miR-200 family member in the subsequence sample above the levels in the first sample, or determining that the brain tumor is regressing or is in remission based on levels of miR-10b miR-21, or miR-200 family member in the subsequent sample below the levels in the first sample.   
     
     
         10 . The method of  claim 9 , wherein:
 the subject has been diagnosed with a primary brain tumor, and the method includes monitoring levels of one or both of miR-10b and miR-21; or   the subject has been diagnosed with a metastatic brain tumor, and the method includes monitoring levels of one or more of miR-10b, miR-21, and a miR-200 family member.   
     
     
         11 . The method of  claim 9 , wherein the method further comprises administering a treatment to the subject after obtaining the first sample and before obtaining the subsequent sample, and wherein a decrease in levels of miR-10b, miR-21, or at least one miR-200 family member in the subsequence sample as compared to the level in the first sample indicates that the treatment is effective. 
     
     
         12 . The method of  claim 11 , wherein the treatment comprises administration of one or more of surgical resection, chemotherapy, or radiotherapy. 
     
     
         13 .- 14 . (canceled) 
     
     
         15 . The method of any of  claim 9 , in which the levels are determined using RT-PCR. 
     
     
         16 . The method of  claim 9 , wherein the miR-200 family member is miR-200a, miR-200b, miR-200c, miR-141, or miR-429. 
     
     
         17 . The method of  claim 9 , wherein the method comprises normalizing the levels to a level of miR-125 or miR-24. 
     
     
         18 . The method of  claim 9 , wherein the primary brain tumor is a glioma, glioblastoma, hemangioma, or medulloblastoma. 
     
     
         19 . (canceled) 
     
     
         20 . A method of treating metastatic or primary brain tumors in a subject, the method comprising:
 determining levels of miR-10b, miR-21, and miR-200 in a sample comprising cerebrospinal fluid (CSF) from a subject, and   comparing the levels of miR-10b, miR-21, and miR-200 to reference levels of miR-10b, miR-21, and at least one miR-200 family member, and   determining that the subject does not have a metastatic or primary brain tumor when the levels of all of miR200, miR-10b or miR-21 are below the reference levels;   diagnosing a metastatic or primary brain tumor in a subject who has levels of miR-10b or miR-21 above the reference levels, and administering a treatment for a metastatic or primary brain tumor to the subject; and   diagnosing a metastatic brain tumor when the levels of the miR-200 family member are above the reference level, and administering a treatment for metastatic brain cancer to a subject who has levels of the miR-200 family member above the reference level.   
     
     
         21 . The method of  claim 20 , wherein determining levels of miR-10b, miR-21, and miR-200 in a sample comprises using real time polymerase chain reaction (RT-PCR) or an RNA expression assay. 
     
     
         22 . The method of  claim 20 , wherein the treatment comprises administration of one or more of surgical resection, chemotherapy, or radiotherapy.