Methods for Diagnosing Lung Cancer using MicroRNAs

Abstract

Described herein are methods for diagnosing lung cancer using microRNAs. Also described are methods and compositions for the diagnosis and treatment of solid cancers. Methods of identifying inhibitors of tumorigenesis are also provided.

What is claimed is: 
     
         1 . A method of diagnosing lung cancer, comprising:
 obtaining a nucleic acid-containing test sample from a subject suspected of having lung cancer, wherein the sample is derived from lung cells;   measuring, by hybridization assay, a level of at least one miR gene product in the test sample; wherein the miR is selected from the group consisting of: miR-21; miR-205; miR-200b; miR-9-1; miR-210; miR-148; miR-141; miR-132; miR-215; miR-128b; let-7g; miR-16-2; miR-129-1/2 prec; miR-126*; miR-142-as; miR-30d; miR-30a-5p; miR-7-2; miR-199a-1; miR-127; miR-34a prec; miR-34a; miR-136; miR-202; miR-196-2; miR-199a-2; let-7a-2; miR-124a-1; miR-149; miR-17-5p; miR-196-1 prec; miR-10a; miR-99b prec; miR-196-1; miR-199b; miR-191; miR-195; and miR-155;   comparing the level of at least one miR gene product in the test sample to a control level of non-cancerous lung cells of at least one corresponding miR gene product; and   diagnosing the subject as having lung cancer, if either the level of the at least one miR gene product in the test sample from the subject is greater than the control level for the corresponding miR gene product, wherein the miR is selected from the group consisting of: miR-21; miR-205; miR-200b; miR-9-1; miR-210; miR-148; miR-141; miR-132; miR-215; miR-128b; let-7g; miR-16-2; miR-129-1/2 prec; miR-142-as; miR-7-2; miR-199a-1; miR-127; miR-34a prec; miR-34a; miR-136; miR-202; miR-196-2; miR-199a-2; let-7a-2; miR-124a-1; miR-149; miR-17-5p; miR-196-1 prec; miR-10a; miR-99b prec; miR-196-1; miR-199b; miR-191; miR-195; and miR-155; or   the level of the at least one miR gene product in the test sample from the subject is lower than the control level for the corresponding miR gene product, wherein the miR is selected from the group consisting of: miR-126*; miR-30d; and miR-30a-5p.   
     
     
         2 . The method of  claim 1 , which further comprises: comparing the level of at least one additional miR gene product in a test sample from the subject to a control level of the miR gene product, wherein the at least one additional miR gene product is selected from the group consisting of: miR-17-5p; miR-191; miR-29b-2; miR-223; miR-128b; miR-199a-1; miR-24-1; miR-24-2; miR-146; miR-155; miR-181b-1; miR-20a; miR-107; miR-32; miR-92-2; miR-214; miR-30c; miR-25; miR-221; and miR-106a. 
     
     
         3 . The method of  claim 1 , which further comprises: comparing the level of at least one additional miR gene product in a test sample from the subject to a control level of the miR gene product, wherein the at least one additional miR gene product is selected from the group consisting of: miR-200b; miR-9-1; miR-210; miR-148; miR-141; miR-132; miR-215; miR-128b; let-7g; miR-16-2; miR-129-1/2 prec; miR-126; miR-142-as; miR-30d; miR-30a-5p; miR-7-2; miR-199a-1; miR-127; miR-34a prec; miR-34a; miR-136; miR-202; miR-196-2; miR-199a-2; let-7a-2; miR-124a-1; miR-149; miR-17-5p; miR-196-1 prec; miR-10a; miR-99b prec; miR-196-1; miR-199b; miR-191; miR-195; and miR-155. 
     
     
         4 . The method of  claim 1 , which further comprises: comparing the level of at least two additional miR gene products in a test sample from the subject to a control level of the corresponding miR gene products, wherein the at least two additional miR gene products are selected from the group consisting of: miR-200b; miR-9-1; miR-148; miR-141; miR-132; miR-215; miR-128b; let-7g; miR-16-2; miR-129-1/2 prec; miR-126; miR-142-as; miR-30d; miR-30a-5p; miR-7-2; miR-199a-1; miR-127; miR-34a prec; miR-34a; miR-136; miR-202; miR-196-2; miR-199a-2; let-7a-2; miR-124a-1; miR-149; miR-17-5p; miR-196-1 prec; miR-10a; miR-99b prec; miR-196-1; miR-199b; miR-191; miR-195; and miR-155. 
     
     
         5 . The method of  claim 1 , which further comprises: comparing the level of at least three additional miR gene products in a test sample from the subject to a control level of the corresponding miR gene products, wherein the at least three additional miR gene products are selected from the group consisting of: miR-200b; miR-9-1; miR-210; miR-148; miR-141; miR-132; miR-215; miR-128b; let-7g; miR-16-2; miR-129-1/2 prec; miR-126; miR-142-as; miR-30d; miR-30a-5p; miR-7-2; miR-199a-1; miR-127; miR-34a prec; miR-34a; miR-136; miR-202; miR-196-2; miR-199a-2; let-7a-2; miR-124a-1; miR-149; miR-17-5p; miR-196-1 prec; miR-10a; miR-99b prec; miR-196-1; miR-199b; miR-191; miR-195; and miR-155. 
     
     
         6 . The method of  claim 1 , which further comprises: comparing the level of at least four additional miR gene products in a test sample from the subject to a control level of the corresponding miR gene products, wherein the at least four additional miR gene products are selected from the group consisting of: miR-200b; miR-9-1; miR-210, miR-148; miR-141; miR-132; miR-215; miR-128b; let-7g; miR-16-2; miR-129-1/2 prec; miR-126; miR-142-as; miR-30d; miR-30a-5p; miR-7-2; miR-199a-1; miR-127; miR-34a prec; miR-34a; miR-136; miR-202; miR-196-2; miR-199a-2; let-7a-2; miR-124a-1; miR-149; miR-17-5p; miR-196-1 prec; miR-10a; miR-99b prec; miR-196-1; miR-199b; miR-191; miR-195; and miR-155. 
     
     
         7 . The method of  claim 1 , which further comprises: comparing the level of at least five additional miR gene products in a test sample from the subject to a control level of the corresponding miR gene products, wherein the at least five additional miR gene products are selected from the group consisting of: miR-200b; miR-9-1; miR-210; miR-148; miR-141; miR-132; miR-215; miR-128b; let-7g; miR-16-2; miR-129-1/2 prec; miR-126; miR-142-as; miR-30d; miR-30a-5p; miR-7-2; miR-199a-1; miR-127; miR-34a prec; miR-34a; miR-136; miR-202; miR-196-2; miR-199a-2; let-7a-2; miR-124a-1; miR-149; miR-17-5p; miR-196-1 prec; miR-10a; miR-99b prec; miR-196-1; miR-199b; miR-191; miR-195; and miR-155. 
     
     
         8 . A method of diagnosing whether a subject has, or is at risk for developing, lung cancer, comprising:
 reverse transcribing at least miR-21 gene product and miR-205 gene product from a test sample from a subject to provide at least two corresponding miR gene product target oligonucleotides;   hybridizing at least miR-21 and miR-205 target oligodeoxynucleotides to a microarray comprising miRNA-specific probe oligonucleotides that include at least one corresponding miR-21 and miR-205 RNA-specific probe oligonucleotides to provide a hybridization profile for the test sample;   comparing the test sample hybridization profile to at least one control hybridization profile; and   diagnosing whether the subject has, or is at risk for developing, lung cancer if the level of at least two corresponding miR gene products in the hybridization profile from the test sample is greater than the control levels of corresponding miR-21 gene product and miR-205 gene product;   wherein the method further comprises comparing a hybridization profile of at least one additional miR gene product in a test sample from the subject to a control hybridization profile of the miR gene product, wherein the at least one additional miR gene product is selected from the group consisting of: miR-17-5p; miR-191; miR-29b-2; miR-223; miR-128b; miR-199a-1; miR-24-1; miR-24-2; miR-146; miR-155; miR-181b-1; miR-20a; miR-107; miR-32; miR-92-2; miR-214; miR-30c; miR-25; miR-221; and miR-106a.   
     
     
         9 . A method of  claim 8 , which further comprises: comparing a hybridization profile of an at least one additional miR gene product in a test sample from the subject to a control hybridization profile of the corresponding miR gene product, wherein the at least one additional miR gene product is selected from the group consisting of: miR-200b; miR-9-1; miR-148; miR-141; miR-132; miR-215; miR-128b; let-7g; miR-16-2; miR-129-1/2 prec; miR-126; miR-142-as; miR-30d; miR-30a-5p; miR-7-2; miR-199a-1; miR-127; miR-34a prec; miR-34a; miR-136; miR-202; miR-196-2; miR-199a-2; let-7a-2; miR-124a-1; miR-149; miR-17-5p; miR-196-1 prec; miR-10a; miR-99b prec; miR-196-1; miR-199b; miR-191; miR-195; and miR-155. 
     
     
         10 . The method of  claim 8 , which further comprises: comparing a hybridization profile of at least two additional miR gene products in a test sample from the subject to a control hybridization profile of the corresponding miR gene products, wherein the at least two additional miR gene products are selected from the group consisting of: miR-200b; miR-9-1; miR-148; miR-141; miR-132; miR-215; miR-128b; let-7g; miR-16-2; miR-129-1/2 prec; miR-126; miR-142-as; miR-30d; miR-30a-5p; miR-7-2; miR-199a-1; miR-127; miR-34a prec; miR-34a; miR-136; miR-202; miR-196-2; miR-199a-2; let-7a-2; miR-124a-1; miR-149; miR-17-5p; miR-196-1 prec; miR-10a; miR-99b prec; miR-196-1; miR-199b; miR-191; miR-195; and miR-155. 
     
     
         11 . The method of  claim 8 , which further comprises: comparing a hybridization profile of at least three additional miR gene products in a test sample from the subject to a control hybridization profile of the corresponding miR gene products, wherein the at least three additional miR gene products are selected from the group consisting of: miR-200b; miR-9-1; miR-148; miR-141; miR-132; miR-215; miR-128b; let-7g; miR-16-2; miR-129-1/2 prec; miR-126; miR-142-as; miR-30d; miR-30a-5p; miR-7-2; miR-199a-1; miR-127; miR-34a prec; miR-34a; miR-136; miR-202; miR-196-2; miR-199a-2; let-7a-2; miR-124a-1; miR-149; miR-17-5p; miR-196-1 prec; miR-10a; miR-99b prec; miR-196-1; miR-199b; miR-191; miR-195; and miR-155. 
     
     
         12 . The method of  claim 8 , which further comprises: comparing a hybridization profile of at least four additional miR gene products in a test sample from the subject to a control hybridization profile of the corresponding miR gene products, wherein the at least four additional miR gene products are selected from the group consisting of: miR-200b; miR-9-1; miR-148; miR-141; miR-132; miR-215; miR-128b; let-7g; miR-16-2; miR-129-1/2 prec; miR-126; miR-142-as; miR-30d; miR-30a-5p; miR-7-2; miR-199a-1; miR-127; miR-34a prec; miR-34a; miR-136; miR-202; miR-196-2; miR-199a-2; let-7a-2; miR-124a-1; miR-149; miR-17-5p; miR-196-1 prec; miR-10a; miR-99b prec; miR-196-1; miR-199b; miR-191; miR-195; and miR-155. 
     
     
         13 . The method of  claim 8 , which further comprises: comparing a hybridization profile of at least five additional miR gene products in a test sample from the subject to a control hybridization profile of the corresponding miR gene products, wherein the at least five additional miR gene products are selected from the group consisting of: miR-200b; miR-9-1; miR-148; miR-141; miR-132; miR-215; miR-128b; let-7g; miR-16-2; miR-129-1/2 prec; miR-126; miR-142-as; miR-30d; miR-30a-5p; miR-7-2; miR-199a-1; miR-127; miR-34a prec; miR-34a; miR-136; miR-202; miR-196-2; miR-199a-2; let-7a-2; miR-124a-1; miR-149; miR-17-5p; miR-196-1 prec; miR-10a; miR-99b prec; miR-196-1; miR-199b; miR-191; miR-195; and miR-155. 
     
     
         14 . A method of inhibiting tumorigenesis in a subject who has lung cancer, comprising:
 determining the amount of at least one miR gene product in cancer cells from the subject, relative to control; and   altering the amount of miR gene product in the cancer cells by:   (i) administering to the subject an effective amount of at least one isolated or synthetic miR gene product, or an isolated variant or biologically-active fragment thereof, wherein the miR is selected from the group consisting of: miR-126*; miR-30d; and miR-30a-5p; or   (ii) administering to the subject an effective amount of at least one compound for inhibiting expression of the at least one miR gene product, wherein the miR is selected from the group consisting of: miR-21; miR-205; miR-200b; miR-9-1; miR-210; miR-148; miR-141; miR-132; miR-215; miR-128b; let-7g; miR-16-2; miR-129-1/2 prec; miR-142-as; miR-7-2; miR-199a-1; miR-127; miR-34a prec; miR-34a; miR-136; miR-202; miR-196-2; miR-199a-2; let-7a-2; miR-124a-1; miR-149; miR-17-5p; miR-196-1 prec; miR-10a; miR-99b prec; miR-196-1; miR-199b; miR-191; miR-195; and miR-155;   such that tumorigenesis is inhibited in the subject.   
     
     
         15 . The method of  claim 1 , further comprising communicating the diagnosis to at least one person. 
     
     
         16 . The method of  claim 8 , further comprising communicating the diagnosis to at least one person.