Methods for identifying risk of breast cancer and treatments thereof
First Claim
1. A method for identifying a subject at risk of breast cancer, which comprises detecting the presence or absence of one or more polymorphic variations associated with breast cancer in a nucleic acid sample from a subject, wherein the one or more polymorphic variations are detected in a nucleotide sequence selected from the group consisting of:
- (a) a nucleotide sequence in SEQ ID NO;
1-5;
(b) a nucleotide sequence which encodes a polypeptide encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(c) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to the amino acid sequence encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(d) a fragment of a nucleotide sequence of (a), (b), or (c);
whereby the presence of the polymorphic variation is indicative of the subject being at risk of breast cancer.
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Accused Products
Abstract
Provided herein are methods for identifying risk of breast cancer in a subject and/or a subject at risk of breast cancer, reagents and kits for carrying out the methods, methods for identifying candidate therapeutics for treating breast cancer, and therapeutic methods for treating breast cancer in a subject. These embodiments are based upon an analysis of polymorphic variations in nucleotide sequences within the human genome.
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Citations
70 Claims
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1. A method for identifying a subject at risk of breast cancer, which comprises detecting the presence or absence of one or more polymorphic variations associated with breast cancer in a nucleic acid sample from a subject, wherein the one or more polymorphic variations are detected in a nucleotide sequence selected from the group consisting of:
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(a) a nucleotide sequence in SEQ ID NO;
1-5;
(b) a nucleotide sequence which encodes a polypeptide encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(c) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to the amino acid sequence encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(d) a fragment of a nucleotide sequence of (a), (b), or (c);
whereby the presence of the polymorphic variation is indicative of the subject being at risk of breast cancer. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 35, 44, 54, 59, 62, 69, 70)
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21. A method for identifying a polymorphic variation associated with breast cancer proximal to an incident polymorphic variation associated with breast cancer, which comprises:
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identifying a polymorphic variation proximal to the incident polymorphic variation associated with breast cancer, wherein the polymorphic variation is detected in a nucleotide sequence selected from the group consisting of;
(a) a nucleotide sequence in SEQ ID NO;
1-5;
(b) a nucleotide sequence which encodes a polypeptide encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(c) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to the amino acid sequence encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(d) a fragment of a nucleotide sequence of (a), (b), or (c) comprising the polymorphic variation;
determining the presence or absence of an association of the proximal polymorphic variant with breast cancer. - View Dependent Claims (23, 24, 25, 26)
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27. An isolated nucleic acid comprising a nucleotide sequence selected from the group consisting of:
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(a) a nucleotide sequence in SEQ ID NO;
1-5;
(b) a nucleotide sequence which encodes a polypeptide encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(c) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to the amino acid sequence encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(d) a fragment of a nucleotide sequence of (a), (b), or (c); and
(e) a nucleotide sequence complementary to the nucleotide sequences of (a), (b), (c), or (d);
wherein the nucleotide sequence comprises one or more polymorphic variants associated with breast cancer selected from the group consisting of an adenine at position 11963 in SEQ ID NO;
1, a guanine at position 36340 in SEQ ID NO;
1, an adenine at position 36992 in SEQ ID NO;
1, a guanine at position 37868 in SEQ ID NO;
1, a cytosine at position 41213 in SEQ ID NO;
1, a guanine at position 41419 in SEQ ID NO;
1, a guanine at position 41613 in SEQ ID NO;
1, a cytosine at position 42407 in SEQ ID NO;
1, a cytosine at position 44247 in SEQ ID NO;
1, an adenine or cytosine at position 44677 in SEQ ID NO;
1, a thymine at position 45256 in SEQ ID NO;
1, a guanine at position 45536 in SEQ ID NO;
1, a cytosine at position 51102 in SEQ ID NO;
1, a guanine at position 72360 in SEQ ID NO;
1, a cytosine at position 36517 in SEQ ID NO;
1, a guanine at position 44677 in SEQ ID NO;
1, a guanine at position 7573 in SEQ ID NO;
2, a cytosine at position 13903 in SEQ ID NO;
2, an adenine at position 23826 in SEQ ID NO;
2, an adenine at position 26057 in SEQ ID NO;
2, a thymine at position 26361 in SEQ ID NO;
2, an adenine at position 26599 in SEQ ID NO;
2, an adenine at position 26812 in SEQ ID NO;
2, a cytosine at position 27069 in SEQ ID NO;
2, an adenine at position 35127 in SEQ ID NO;
2, a thymine at position 35222 in SEQ ID NO;
2, a cytosine at position 36424 in SEQ ID NO;
2, a cytosine at position 46176 in SEQ ID NO;
2, a cytosine at position 50452 in SEQ ID NO;
2, a guanine at position 61093 in SEQ ID NO;
2, an adenine at position 62572 in SEQ ID NO;
2, a guanine at position 70759 in SEQ ID NO;
2, an adenine at position 107 in SEQ ID NO;
3, a thymine at position 14361 in SEQ ID NO;
3, a guanine at position 19365 in SEQ ID NO;
3, a thymine at position 42164 in SEQ ID NO;
3, a cytosine at position 45031 in SEQ ID NO;
3, a thymine at position 45655 in SEQ ID NO;
3, a cytosine at position 48563 in SEQ ID NO;
3, a thymine at position 174 in SEQ ID NO;
4, an adenine at position 815 in SEQ ID NO;
4, a cytosine at position 3480 in SEQ ID NO;
4, a guanine at position 19834 in SEQ ID NO;
4, an adenine at position 19850 in SEQ ID NO;
4, a thymine at position 20171 in SEQ ID NO;
4, a thymine at position 20500 in SEQ ID NO;
4, a cytosine at position 20536 in SEQ ID NO;
4, a cytosine at position 23187 in SEQ ID NO;
4, a thymine at position 25470 in SEQ ID NO;
4, a thymine at position 30155 in SEQ ID NO;
4, a guanine at position 30752 in SEQ ID NO;
4, a thymine at position 32710 in SEQ ID NO;
4, a guanine at position 32954 in SEQ ID NO;
4, an adenine at position 38115 in SEQ ID NO;
4, a cytosine at position 39150 in SEQ ID NO;
4, a thymine at position 40840 in SEQ ID NO;
4, an adenine at position 41969 in SEQ ID NO;
4, a thymine at position 42045 in SEQ ID NO;
4, a guanine at position 43785 in SEQ ID NO;
4, a cytosine at position 45386 in SEQ ID NO;
4, an adenine at position 46827 in SEQ ID NO;
4, an adenine at position 47320 in SEQ ID NO;
4, a cytosine at position 47625 in SEQ ID NO;
4, a cytosine at position 47837 in SEQ ID NO;
4, an adenine at position 47866 in SEQ ID NO;
4, a cytosine at position 49002 in SEQ ID NO;
4, a thymine at position 49566 in SEQ ID NO;
4, a cytosine at position 52058 in SEQ ID NO;
4, a thymine at position 52257 in SEQ ID NO;
4, a thymine at position 52850 in SEQ ID NO;
4, a cytosine at position 53860 in SEQ ID NO;
4, a cytosine at position 54052 in SEQ ID NO;
4, a thymine at position 54411 in SEQ ID NO;
4, a cytosine at position 55303 in SEQ ID NO;
4, an adenine at position 59398 in SEQ ID NO;
4, an adenine at position 60542 in SEQ ID NO;
4, an adenine at position 62309 in SEQ ID NO;
4, a cytosine at position 72299 in SEQ ID NO;
4, a thymine at position 73031 in SEQ ID NO;
4, a guanine at position 73803 in SEQ ID NO;
4, and a thymine at position 98116, and an adenine at position 174 in SEQ ID NO;
5. - View Dependent Claims (28, 29, 30)
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31. A method for identifying a candidate molecule that modulates cell proliferation, which comprises:
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(a) introducing a test molecule to a system which comprises a nucleic acid comprising a nucleotide sequence selected from the group consisting of;
(i) a nucleotide sequence in SEQ ID NO;
1-5;
(ii) a nucleotide sequence which encodes a polypeptide encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(iii) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to the amino acid sequence encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(iv) a fragment of a nucleotide sequence of (i), (ii), or (iii);
orintroducing a test molecule to a system which comprises a protein encoded by a nucleotide sequence of (i), (ii), (iii), or (iv); and
(b) determining the presence or absence of an interaction between the test molecule and the nucleic acid or protein, whereby the presence of an interaction between the test molecule and the nucleic acid or protein identifies the test molecule as a candidate molecule that modulates cell proliferation. - View Dependent Claims (32, 33, 34, 36)
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37. A method for identifying a candidate therapeutic for treating breast cancer, which comprises:
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(a) introducing a test molecule to a system which comprises a nucleic acid comprising a nucleotide sequence selected from the group consisting of;
(i) a nucleotide sequence in SEQ ID NO;
1-5;
(ii) a nucleotide sequence which encodes a polypeptide encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(iii) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to the amino acid sequence encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(iv) a fragment of a nucleotide sequence of (i), (ii), or (iii);
orintroducing a test molecule to a system which comprises a protein encoded by a nucleotide sequence of (i), (ii), (iii), or (iv); and
(b) determining the presence or absence of an interaction between the test molecule and the nucleic acid or protein, whereby the presence of an interaction between the test molecule and the nucleic acid or protein identifies the test molecule as a candidate therapeutic for treating breast cancer. - View Dependent Claims (38)
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39. A method for treating breast cancer in a subject, which comprises contacting one or more cells of a subject in need thereof with a nucleic acid, wherein the nucleic acid comprises a nucleotide sequence selected from the group consisting of:
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(a) a nucleotide sequence in SEQ ID NO;
1-5;
(b) a nucleotide sequence which encodes a polypeptide encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(c) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to the amino acid sequence encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(d) a fragment of a nucleotide sequence of (a), (b), or (c); and
(e) a nucleotide sequence complementary to the nucleotide sequences of (a), (b), (c), or (d);
whereby contacting the one or more cells of the subject with the nucleic acid treats breast cancer in the subject. - View Dependent Claims (40, 41, 42)
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43. A method for treating breast cancer in a subject, which comprises:
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detecting the presence or absence of one or more polymorphic variations associated with breast cancer in a nucleic acid sample from a subject, wherein the one or more polymorphic variation are detected in a nucleotide sequence selected from the group consisting of;
(a) a nucleotide sequence in SEQ ID NO;
1-5;
(b) a nucleotide sequence which encodes a polypeptide encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(c) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to the amino acid sequence encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(d) a fragment of a nucleotide sequence of (a), (b), or (c) comprising the polymorphic variation; and
administering a breast cancer treatment to a subject in need thereof based upon the presence or absence of the one or more polymorphic variations in the nucleic acid sample. - View Dependent Claims (45, 46, 47, 48, 49, 50, 51, 52)
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53. A method for detecting or preventing breast cancer in a subject, which comprises:
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detecting the presence or absence of one or more polymorphic variations associated with breast cancer in a nucleic acid sample from a subject, wherein the polymorphic variation is detected in a nucleotide sequence selected from the group consisting of;
(a) a nucleotide sequence in SEQ ID NO;
1-5;
(b) a nucleotide sequence which encodes a polypeptide encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(c) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to the amino acid sequence encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(d) a fragment of a nucleotide sequence of (a), (b), or (c) comprising the polymorphic variation; and
administering a breast cancer prevention procedure or detection procedure to a subject in need thereof based upon the presence or absence of the one or more polymorphic variations in the nucleic acid sample. - View Dependent Claims (55, 56, 57)
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58. A method of targeting information for preventing or treating breast cancer to a subject in need thereof, which comprises:
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detecting the presence or absence of one or more polymorphic variations associated with breast cancer in a nucleic acid sample from a subject, wherein the polymorphic variation is detected in a nucleotide sequence selected from the group consisting of;
(a) a nucleotide sequence in SEQ ID NO;
1-5;
(b) a nucleotide sequence which encodes a polypeptide encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(c) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to the amino acid sequence encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(d) a fragment of a nucleotide sequence of (a), (b), or (c) comprising the polymorphic variation; and
directing information for preventing or treating breast cancer to a subject in need thereof based upon the presence or absence of the one or more polymorphic variations in the nucleic acid sample. - View Dependent Claims (60)
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61. A method of selecting a subject that will respond to a treatment of breast cancer, which comprises:
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detecting the presence or absence of one or more polymorphic variations associated with breast cancer in a nucleic acid sample from a subject, wherein the polymorphic variation is detected in a nucleotide sequence selected from the group consisting of;
(a) the nucleotide sequence of SEQ ID NO;
1-5;
(b) a nucleotide sequence which encodes a polypeptide consisting of an amino acid sequence encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(c) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to an amino acid sequence encoded by a nucleotide sequence in SEQ ID NO;
1-5; and
(d) a fragment of a nucleotide sequence of (a), (b), or (c) comprising the polymorphic variation; and
selecting a subject that will respond to the breast cancer treatment based upon the presence or absence of the one or more polymorphic variations in the nucleic acid sample.
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- 63. A composition comprising a breast cancer cell and an antibody that specifically binds to a protein, polypeptide or peptide encoded by a nucleotide sequence identical to or 90% or more identical to a nucleotide sequence in SEQ ID NO:
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65. A composition comprising a breast cancer cell and a RNA, DNA, PNA or ribozyme molecule comprising a nucleotide sequence identical to or 90% or more identical to a portion of a nucleotide sequence in SEQ ID NO:
- 1-12.
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67. A method for determining a risk of breast cancer in a subject, which comprises detecting the presence or absence of two or more polymorphic variations associated with breast cancer in a nucleic acid sample from a subject, wherein two or more of the polymorphic variations are detected in a nucleotide sequence selected from the group consisting of:
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(a) a nucleotide sequence in SEQ ID NO;
1-5;
(b) a nucleotide sequence which encodes a polypeptide encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(c) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to the amino acid sequence encoded by a nucleotide sequence in SEQ ID NO;
1-5;
(d) a fragment of a nucleotide sequence of (a), (b), or (c);
whereby the presence of the polymorphic variation is indicative of the subject being at risk of breast cancer. - View Dependent Claims (68)
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Specification