Methods for Diagnosing Breast Cancer Using miR-21, miR-125-1, miR-125b-2 and miR-145
The present invention provides novel methods and compositions for the diagnosis and treatment of solid cancers. The invention also provides methods of identifying inhibitors of tumorigenesis.
1 .- 33 . (canceled)
34 . A method of diagnosing whether a subject has, or is at risk for developing breast cancer, comprising:
a.) comparing the level of at least miR-21 gene product in a test sample to a control level of at least miR-21 gene product; and
b.) diagnosing whether the subject has, or is at risk for developing, breast cancer if the level of at least miR-21 gene product in the test sample from the subject is greater than the level of miR-21 gene product of the control.
35 . A method of diagnosing whether a subject has, or is at risk for developing breast cancer, comprising:
a.) reverse transcribing at least miR-21 from a test sample obtained from the subject to provide at least miR-21 target oligonucleotides;
b.) hybridizing at least the miR-21 target oligodeoxynucleotides to a microarray comprising miRNA-specific probe oligonucleotides that include at least miR-21 RNA specific probe oligonucleotides to provide a hybridization profile for the test sample;
c.) comparing the test sample hybridization profile to at least one control hybridization profile; and
d.) diagnosing whether the subject has, or is at risk for developing, breast cancer if the level of at least miR-21 gene products in the test sample from the subject is greater than the level of miR-21 gene products of the control.
36 . The method of claim 34 , 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-21; 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.
37 . The method of claim 34 , 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-21; 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.
38 . The method of claim 34 , 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-21; 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.
39 . The method of claim 34 , 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-21; 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.
40 . The method of claim 34 , 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-21; 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.
41 . The method of claim 34 , which further comprises comparing the level of at least miR-125-1 gene product in a test sample from the subject to a control level of miR-125-1 gene product.
42 . The method of claim 34 , which further comprises comparing the level of at least miR-125-2 gene product in a test sample from the subject to a control level of miR-125-2 gene product.
43 . The method of claim 34 , which further comprises comparing the level of at least miR-145 gene product in a test sample from the subject to a control level of miR-145 gene product.
44 . The method of claim 34 , 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 corresponding miR gene products, wherein the at least one additional miR gene product is selected from the group consisting of: miR-21; miR-29b-2; miR-146; miR-125b-2; miR-125b-1; miR-10b; miR-145; miR-181a; miR-140; miR-213; miR-29a prec; miR-181b-1; miR-199b; miR-29b-1; miR-130a; miR-155; let-7a-2; miR-205; miR-29c; miR-224; miR-100; miR-31; miR-30c; miR-17-5p; miR-210; miR-122a; and miR-16-2.
45 . A method of diagnosing whether a subject has, or is at risk for developing breast cancer, comprising:
a.) comparing the level of at least miR-125-1 gene product in a test sample to a control level of at least miR-125-1 gene product; and
b.) diagnosing whether the subject has, or is at risk for developing, breast cancer if the level of at least miR-125-1 gene product in the test sample from the subject is greater than the level of miR-125-1 gene product of the control.
46 . A method of diagnosing whether a subject has, or is at risk for developing breast cancer, comprising:
a.) reverse transcribing at least miR-125-1 from a test sample obtained from the subject to provide at least miR-125-1 target oligonucleotides;
b.) hybridizing at least the miR-125-1 target oligodeoxynucleotides to a microarray comprising miRNA-specific probe oligonucleotides that include at least miR-125-1 RNA specific probe oligonucleotides to provide a hybridization profile for the test sample;
c.) comparing the test sample hybridization profile to at least one control hybridization profile; and
d.) diagnosing whether the subject has, or is at risk for developing, breast cancer if the level of at least miR-125-1 gene products in the test sample from the subject is greater than the level of miR-125-1 gene products of the control.
47 . The method of claim 45 , 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-21; 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.
48 . The method of claim 45 , 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-21; 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.
49 . The method of claim 45 , 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-21; 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.
50 . The method of claim 45 , 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-21; 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.
51 . The method of claim 45 , 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-21; 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.
52 . The method of claim 45 , which further comprises comparing the level of at least miR-125-2 gene product in a test sample from the subject to a control level of miR-125-2 gene product.
53 . The method of claim 45 , which further comprises comparing the level of at least miR-145 gene product in a test sample from the subject to a control level of miR-145 gene product.
54 . The method of claim 45 , 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 corresponding miR gene products, wherein the at least one additional miR gene product is selected from the group consisting of: miR-21; miR-29b-2; miR-146; miR-125b-2; miR-125b-1; miR-10b; miR-145; miR-181a; miR-140; miR-213; miR-29a prec; miR-181b-1; miR-199b; miR-29b-1; miR-130a; miR-155; let-7a-2; miR-205; miR-29c; miR-224; miR-100; miR-31; miR-30c; miR-17-5p; miR-210; miR-122a; and miR-16-2.
55 . A method of diagnosing whether a subject has, or is at risk for developing breast cancer, comprising:
a.) reverse transcribing at least miR-125b-2 from a test sample obtained from the subject to provide at least miR-125b-2 target oligonucleotides;
b.) hybridizing at least the miR-125b-2 target oligodeoxynucleotides to a microarray comprising miRNA-specific probe oligonucleotides that include at least miR-125b-2 RNA specific probe oligonucleotides to provide a hybridization profile for the test sample;
c.) comparing the test sample hybridization profile to at least one control hybridization profile; and
d.) diagnosing whether the subject has, or is at risk for developing, breast cancer if the level of at least miR-125b-2 gene products in the test sample from the subject is greater than the level of miR-125b-2 gene products of the control.
56 . The method of claim 55 , 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-21; 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.
57 . The method of claim 55 , 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-21; 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.
58 . The method of claim 55 , 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-21; 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.
59 . The method of claim 55 , 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-21; 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.
60 . The method of claim 55 , 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-21; 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.
61 . The method of claim 55 , which further comprises comparing the level of at least miR-145 gene product in a test sample from the subject to a control level of miR-145 gene product.
62 . The method of claim 55 , 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 corresponding miR gene products, wherein the at least one additional miR gene product is selected from the group consisting of: miR-21; miR-29b-2; miR-146; miR-125b-2; miR-125b-1; miR-10b; miR-145; miR-181a; miR-140; miR-213; miR-29a prec; miR-181b-1; miR-199b; miR-29b-1; miR-130a; miR-155; let-7a-2; miR-205; miR-29c; miR-224; miR-100; miR-31; miR-30c; miR-17-5p; miR-210; miR-122a; and miR-16-2.
63 . A method of diagnosing whether a subject has, or is at risk for developing breast cancer, comprising:
a.) reverse transcribing at least miR-145 from a test sample obtained from the subject to provide at least miR-145 target oligonucleotides;
b.) hybridizing at least the miR-145 target oligodeoxynucleotides to a microarray comprising miRNA-specific probe oligonucleotides that include at least miR-145 RNA specific probe oligonucleotides to provide a hybridization profile for the test sample;
c.) comparing the test sample hybridization profile to at least one control hybridization profile; and
d.) diagnosing whether the subject has, or is at risk for developing, breast cancer if the level of at least miR-145 gene products in the test sample from the subject is greater than the level of miR-145 gene products of the control.
64 . The method of claim 63 , 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-21; 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.
65 . The method of claim 63 , 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-21; 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.
66 . The method of claim 63 , 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-21; 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.
67 . The method of claim 63 , 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-21; 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.
68 . The method of claim 63 , 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-21; 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.
69 . The method of claim 63 , 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 corresponding miR gene products, wherein the at least one additional miR gene product is selected from the group consisting of: miR-21; miR-29b-2; miR-146; miR-125b-2; miR-125b-1; miR-10b; miR-145; miR-181a; miR-140; miR-213; miR-29a prec; miR-181b-1; miR-199b; miR-29b-1; miR-130a; miR-155; let-7a-2; miR-205; miR-29c; miR-224; miR-100; miR-31; miR-30c; miR-17-5p; miR-210; miR-122a; and miR-16-2.