Methods and compositions for diagnosing and predicting the behavior of cancer
First Claim
Patent Images
1. A method of determining the metastatic potential of a tumor comprising:
- (a) contacting a tumor sample, or isolate thereof, with an antibody that specifically binds to a human SIX1 polypeptide or a nucleic acid probe that specifically hybridizes to a human SIX1 nucleic acid molecule under stringent conditions, comprising hybridization in 6X SSC at about 45°
C., followed by one or more washes in 0.2X SSC, 0.1% SPS at 50–
65°
C., such that expression of the SIX1 polypeptide or nucleic acid molecule is detected in the tumor sample or isolate; and
(b) comparing the expression of SIX1 in the sample or isolate to a standard or control, wherein increased expression of SIX1 relative to the standard or control is determinative of the metastatic potential of the tumor,wherein the antibody specifically binds to a polypeptide selected from the group consisting of;
(1) a polypeptide comprising SEQ ID NO;
2;
(2) a polypeptide comprising at least amino acids 183–
284 of SEQ ID NO;
2, which is at least 95% homologous to SEQ ID NO;
2, and has the ability to enhance cell cycle progression; and
(3) a polypeptide consisting of amino acids 183–
284 of SEQ ID NO;
2; and
wherein the human SIX1 nucleic acid molecule encodes a biologically active human SIX1 polypeptide, and is selected from the group consisting of a nucleic acid molecule consisting of the nucleotide sequence of SEQ ID NO;
1, a nucleic acid molecule comprising at least nucleotides 276 to 1130 of SEQ ID NO;
1, and a nucleic acid molecule encoding a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2.
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Abstract
The present invention relates to methods for detecting the presence of SIX1 protein or nucleic acid in a biological sample in which a biological sample is contacted with an agent capable of detecting SIX1 protein or mRNA such that the presence of SIX1 is detected in the biological sample. Diagnostic and prognostic methods utilizing HSIX1 as an indicator of cancer and cancer progression are also provided. Compositions and kits for detecting the presence of SIX1 in a biological sample are also described.
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Citations
26 Claims
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1. A method of determining the metastatic potential of a tumor comprising:
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(a) contacting a tumor sample, or isolate thereof, with an antibody that specifically binds to a human SIX1 polypeptide or a nucleic acid probe that specifically hybridizes to a human SIX1 nucleic acid molecule under stringent conditions, comprising hybridization in 6X SSC at about 45°
C., followed by one or more washes in 0.2X SSC, 0.1% SPS at 50–
65°
C., such that expression of the SIX1 polypeptide or nucleic acid molecule is detected in the tumor sample or isolate; and(b) comparing the expression of SIX1 in the sample or isolate to a standard or control, wherein increased expression of SIX1 relative to the standard or control is determinative of the metastatic potential of the tumor, wherein the antibody specifically binds to a polypeptide selected from the group consisting of; (1) a polypeptide comprising SEQ ID NO;
2;(2) a polypeptide comprising at least amino acids 183–
284 of SEQ ID NO;
2, which is at least 95% homologous to SEQ ID NO;
2, and has the ability to enhance cell cycle progression; and(3) a polypeptide consisting of amino acids 183–
284 of SEQ ID NO;
2; andwherein the human SIX1 nucleic acid molecule encodes a biologically active human SIX1 polypeptide, and is selected from the group consisting of a nucleic acid molecule consisting of the nucleotide sequence of SEQ ID NO;
1, a nucleic acid molecule comprising at least nucleotides 276 to 1130 of SEQ ID NO;
1, and a nucleic acid molecule encoding a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2. - View Dependent Claims (15, 16, 17, 25, 26)
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2. A prognostic method for determining whether a subject is at risk for developing cancer comprising:
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(a) contacting a biological sample obtained from the subject, or isolate of the sample, with an antibody that specifically binds to a human SIX1 polypeptide or a nucleic acid probe that specifically hybridizes to a human SIX1 nucleic acid molecule under stringent conditions, comprising hybridization in 6X SSC at about 45°
C. followed by one or more washes in 0.2X SSC, 0.1% SDS at 505°
C., such that expression of the SIX1 polypeptide or nucleic acid molecule is detected in the sample or isolate; and(b) comparing the expression of SIX1 in the sample or isolate to a standard or control, wherein increased expression of SIX1 relative to the standard or control is determinative of the subject being at risk for developing cancer, wherein the antibody specifically binds to a polypeptide selected from the group consisting of; (1) a polypeptide comprising SEQ ID NO;
2;(2) a polypeptide comprising at least amino acids 182–
284 of SEQ ID NO;
2, which is at least 95% homologous to SEQ ID NO;
2, and has the ability to enhance cell-cycle progression; and(3) a polypeptide consisting of amino acids 183–
284 of SEQ ID NO;
2; andwherein the human SIX1 nucleic acid molecule encodes a biologically active human SIX1 polypeptide, and is selected from the group consisting of a nucleic acid molecule consisting of the nucleotide sequence of SEQ ID NO;
1, a nucleic acid molecule comprising at least nucleotides 276 to 1130 of SEQ ID NO;
1, a nucleic acid molecule consisting of nucleotides 276 to 1130 of SEQ ID NO;
1, and a nucleic acid molecule encoding a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2. - View Dependent Claims (7, 9, 10, 11, 12, 18, 19, 20, 21, 22, 23, 24)
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3. A method for diagnosis of a tumor comprising:
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(a) contacting a suspected tumor sample, or isolate thereof, with an antibody capable that specifically binds to a human SIX1 polypeptide or a nucleic acid probe that specifically hybridizes to a human SIX1 nucleic acid molecule under stringent conditions, comprising hybridizaton in, 6X SSC at about 45°
C. followed by one or more washes in 0.2X SSC, 0.1% SDS at 50–
65°
C., such that expression of the SDC1 polypeptide or nucleic acid molecule is detected in the sample or isolate; and(b) comparing the expression of SIX1 in the sample or isolate to a standard or control, wherein increased expression of SIX1 relative to the standard or control is diagnostic of the tumor, wherein the antibody specifically binds to a polypeptide selected from the group consisting of; (1) a polypeptide comprising SEQ ID NO;
2;(2) a polypeptide comprising at least amino acids 183–
284 of SEQ ID NO;
2. which is at least 95% homologous to SEQ ID NO;
2, and has the ability to enhance cell cycle progression; and(3) a polypeptide consisting of amino acids 183–
284 of SEQ ID NO;
2; andwherein the human SIX1 nucleic acid molecule encodes a biologically active human SIX1 polypeptide, and is selected from the group consisting of a nucleic acid molecule consisting of the nucleotide sequence of SEQ ID NO;
1, a nucleic acid molecule comprising at least nucleotides 276 to 1130 of SEQ ID NO;
1, a nucleic acid molecule consisting of nucleotides 276 to 1130 of SEQ ID NO;
1, and a nucleic acid molecule encoding a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2.
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4. A method of diagnosing cancer in a subject comprising:
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(a) contacting a biological sample obtained from the subject, or isolate of the sample, with an antibody that specifically binds to a human SIX1 polypeptide or a nucleic acid probe that specifically hybridizes to a human SIX1 nucleic acid molecule under stringent conditions, comprising hybridization in 6X SSC at about 45°
C., followed by one or more washes in 0.2X SSC, 0.1% SDS at 50–
65°
C., such that expression of the SIX1 polypeptide or nucleic acid molecule is detected in the sample or isolate; and(b) comparing the expression of SIX1 in the sample or isolate to a standard or control, wherein increased expression, of SIX1 relative to the standard or control is diagnostic of cancer in the subject, wherein the antibody specifically binds to a polypeptide selected from the group consisting of; (1) a polypeptide comprising SEQ ID NO;
2;(2) a polypeptide comprising at least amino acids 183–
284 of SEQ ID NO;
2, which is at least 95% homologous to SEQ ID NO;
2, and has the ability to enhance cell cycle progression; and(3) a polypeptide consisting of amino acids 183–
284 of SEQ ID NO;
2; andwherein the human SIX1 nucleic acid molecule encodes a biologically active human SIX1 polypeptide, and is selected from the group consisting of a nucleic acid molecule consisting of the nucleotide sequence of SEQ ID NO;
1, a nucleic acid molecule comprising at least nucleotides 276 to 1130 of SEQ ID NO;
1, a nucleic acid molecule consisting of nucleotides 276 to 1130 of SEQ ID NO;
1, and a nucleic acid molecule encoding a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2.
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5. A method for monitoring the progression of cancer in a patient comprising:
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(a) contacting a biological sample obtained from the patient, or isolate of the sample, with an antibody that specifically binds to a human SIX1 polypeptide such that expression of the SIX1 polypeptide is detected in the biological sample; and (b) comparing the expression of SIX1 in the sample to a standard or control, wherein increased expression of SIX1 relative to the standard or control is an indicator of cancer progression, and wherein the SIX1 polypeptide is selected from the group consisting of; (1) a polypeptide comprising SEQ ID NO;
2;(2) a polypeptide comprising at least amino acids 183–
284 of SEQ ID NO;
2, which is at least 95% homologous to SEQ ID NO;
2, and has the ability to enhance cell cycle progression; and(3) a polypeptide consisting of amino acids 183–
284 of SEQ ID NO;
2. - View Dependent Claims (13, 14)
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6. A method for monitoring the progression of cancer in a patient comprising:
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(a) contacting a biological sample obtained from the patient, or isolate of the sample, with a nucleic acid probe that specifically hybridizes to a human SIX1 nucleic acid molecule under stringent conditions, comprising hybridization in 6X SSC at about 45°
C., followed by one or more washes in 0.2X SSC, 0.1% SDS at 50–
65°
C. such that expression of the nucleic acid molecule is detected in the biological sample; and(b) comparing the expression of SIX1 in the sample to a standard or control, wherein increased expression of SIX1 relative to the standard or control is an indicator of cancer progression, and wherein the nucleic acid molecule encodes a biologically active human SIX1 polypeptide, and is selected from the group consisting of a nucleic acid molecule consisting of the nucleotide sequence of SEQ ID NO;
1, a nucleic acid molecule comprising at least nucleotides 276 to 1130 of SEQ ID NO, 1, a nucleic acid molecule consisting of at least nucleotides 276 to 1130 of SEQ ID NO;
1, and a nucleic acid molecule encoding a polypeptide consisting of the amino acid sequence of SEQ ID NO;
2.
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8. The method of claim, wherein the tissue sample is derived from the pancreas, stomach, liver, secretory gland, bladder, lung, skin, prostate gland, ovary, cervix, uterus, brain, eye, connective tissue, bone, muscles or vasculature.
Specification