Micrornas expression signature for determination of tumors origin

Abstract

The present invention provides a process for classification of specific cancers and tumors origin through the analysis of the expression patterns of specific microRNAs and nucleic acid molecules relating thereto. Classification according to a microRNA expression framework allows optimization of treatment, and determination of specific therapy.

1 . A method of classifying a cancer selected from the group consisting of liver cancer, brain cancer and gastrointestinal (GI) cancer, said method comprising:
 (a) obtaining a biological sample from a subject;   (b) determining an expression profile of a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 1-33, a fragment thereof and a sequence having at least about 80% identity thereto from said sample; and   (c) comparing said expression profile to a reference expression profile, wherein the results of said comparison allows for classification of said specific cancer.   
     
     
         2 . The method of  claim 1 , wherein said liver cancer is hepatocellular carcinoma (HCC). 
     
     
         3 . The method of  claim 1 , wherein said gastrointestinal (GI) cancer is selected from the group consisting of colon, pancreas and stomach cancer. 
     
     
         4 . The method of  claim 1 , wherein said brain cancer is selected from the group consisting of glioblastoma, astrocytoma and oligodendroglioma. 
     
     
         5 . The method of  claim 1 , wherein said biological sample is selected from the group consisting of bodily fluid, a cell line and a tissue sample. 
     
     
         6 . The method of  claim 5 , wherein said tissue is a fresh, frozen, fixed, wax-embedded or formalin fixed paraffin-embedded (FFPE) tissue. 
     
     
         7 . The method of  claim 1 , wherein said method further comprises a classifier algorithm. 
     
     
         8 . The method of  claim 7 , wherein said classifier is selected from the group consisting of decision tree classifier, logistic regression classifier, nearest neighbor classifier, neural network classifier, Gaussian mixture model (GMM) and Support Vector Machine (SVM) classifier. 
     
     
         9 . The method of  claim 1  for classifying liver cancer, the method comprising determining an expression profile of a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 6-13, 32-33, a fragment thereof and a sequence having at least about 80% identity thereto from said sample; and comparing said expression profile to a reference expression profile, wherein the results of said comparison allows for classifying said liver cancer. 
     
     
         10 . A method to distinguish between hepatocellular carcimoma (HCC) and metastasis to the liver, the method comprising obtaining a biological sample from a subject; determining an expression profile of a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 6-13, 32-33, a fragment thereof and a sequence having at least about 80% identity thereto from said sample; and comparing said expression profile to a reference expression profile, wherein said comparison is indicative of hepatocellular carcimoma (HCC) or metastasis to the liver. 
     
     
         11 . The method of  claim 10 , wherein the metastasis to the liver is adenocarcinoma. 
     
     
         12 . The method of  claim 1  for classifying brain cancer, the method comprising determining an expression profile of a nucleic acid sequence selected from the group consisting of SEQ ID NOS: -1427, a fragment thereof and a sequence having at least about 80% identity thereto from said sample; and comparing said expression profile to a reference expression profile, wherein the results of said comparison allows for classifying said brain cancer. 
     
     
         13 . A method to distinguish between brain cancer and metastasis to the brain, the method comprising obtaining a biological sample from a subject; determining an expression profile of a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 14-27, a fragment thereof and a sequence having at least about 80% identity thereto from said sample and comparing said expression profile to a reference expression profile, wherein said comparison is indicative of brain cancer and metastasis to brain. 
     
     
         14 . The method of  claim 1  for identifying gastrointestinal (GI) cancer, the method comprising determining an expression profile of a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 5-1, a fragment thereof and a sequence having at least about 80% identity thereto from said sample; and comparing said expression profile to a reference expression profile, wherein the results of said comparison allows for classifying said GI cancer 
     
     
         15 . A method to distinguish between primary GI and non-GI tumor, the method comprising obtaining a biological sample from a subject; determining an expression profile of a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 5-1, a fragment thereof and a sequence having at least about 80% identity thereto from said sample; and comparing said expression profile to a reference expression profile, wherein said comparison is indicative of primary GI or non-GI tumor. 
     
     
         16 . The method of  claim 15 , wherein said primary GI tumor is selected from the group consisting of colon, pancreas and stomach tumor. 
     
     
         17 . The method of  claim 15 , wherein said non-GI tumor is selected from the group consisting of lung and breast tumor. 
     
     
         18 . A kit for cancer classification, wherein said cancer is selected from the group consisting of liver cancer, brain cancer and gastrointestinal (GI) cancer said kit comprising a probe comprising a nucleic acid that is complementary to a sequence selected from the group consisting of SEQ ID NOS: 1-27, 32-33; a fragment thereof, and a sequence having at least about 80% identity thereto. 
     
     
         19 . The kit of  claim 18 , wherein said cancer is brain cancer and said probe comprises a sequence selected from the group consisting of SEQ ID NOS: 39-43, a fragment thereof, and a sequence having at least about 80% identity thereto. 
     
     
         20 . The kit of  claim 19 , wherein the kit further comprises a forward primer selected from the group consisting of SEQ ID NOS: 34-38, a fragment thereof, and a sequence having at least about 80% identity thereto and a reverse primer comprising SEQ ID NO: 44.