US 2004/0110668 A1 · Nucleic acid sequences differentially expressed in cancer tissue

Abstract

This invention relates to novel nucleic acid sequences which are differentially expressed in cancer cells. The invention also relates to proteins and peptides encoded by the sequences, to diagnostic assays and therapeutic agents based on the sequences and proteins, and to probes, antisense constructs, and antibodies derived from the sequences and proteins or peptides. The subject nucleic acids have been found to be differentially expressed by tumor cells, particularly in colon cancer tissue.

Claims42

Dependent claims

An isolated nucleic acid comprising SEQ ID Nos 1-503 or a sequence complementary thereto.

An isolated nucleic acid comprising a nucleotide sequence which hybridizes under stringent conditions to a sequence of SEQ ID Nos. 1-503 or a sequence complementary thereto.

An isolated nucleic acid comprising a nucleotide sequence at least 80% identical to a sequence corresponding to at least about 15 consecutive nucleotides of one of SEQ ID Nos. 1-503 or a sequence complementary thereto.

A substantially pure nucleic acid which hybridizes under stringent conditions to a nucleic acid probe corresponding to at least 12 consecutive nucleotides of one of SEQ ID Nos. 1-1103 or a sequence complementary thereto.

A probe/primer comprising a substantially purified oligonucleotide, said oligonucleotide containing a region of nucleotide sequence which hybridizes under stringent conditions to at least 12 consecutive nucleotides of sense or antisense sequence selected from SEQ ID Nos. 1-1103.

An antisense oligonucleotide analog which hybridizes under stringent conditions to at least 12 consecutive nucleotides of one of SEQ ID Nos. 1-503 or a sequence complementary thereto, and which is resistant to cleavage by a nuclease.

A test kit for determining the phenotype of transformed cells, comprising an antibody specific for a protein encoded by a nucleic acid which hybridizes under stringent conditions to any one of SEQ Nos. 1-4470.

A method of determining the phenotype of a cell, comprising detecting the differential expression, relative to a normal cell, of at least one nucleic acid which hybridizes under stringent conditions to one of SEQ ID Nos. 1-4470, 4472, 4474, 4476, 4478, 4480, 4482, 4484, 4486, 4488, 4490, 4492, and 4494, wherein the nucleic acid is differentially expressed by at least a factor of two.

A method for determining the phenotype of cells in a sample of cells from a patient, comprising:

(a) providing a nucleic acid probe comprising a nucleotide sequence having at least 12 consecutive nucleotides of any of SEQ ID Nos. 1-4470, 4472, 4474, 4476, 4478, 4480, 4482, 4484, 4486, 4488, 4490, 4492, and 4494;
(b) obtaining a sample of cells from a patient;
(c) providing a second sample of cells substantially all of which are non-cancerous;
(d) contacting the nucleic acid probe under stringent conditions with mRNA of each of said first and second cell samples;
and comparing (a) the amount of hybridization of the probe with mRNA of the first cell sample, with (b) the amount of hybridization of the probe with mRNA of the second cell sample, wherein a difference of at least a factor of two in the amount of hybridization with the mRNA of the first cell sample as compared to the amount of hybridization with the mRNA of the second cell sample is indicative of the phenotype of cells in the first cell sample.

2 more elements

A method of determining the phenotype of cell, comprising detecting the differential expression, relative to a normal cell, of at least one polypeptide encoded by a nucleic acid which hybridizes under stringent conditions to one of SEQ ID Nos. 1-4470, wherein the polypeptide is differentially expressed by at least a factor of two.

A method of determining the phenotype of cell, comprising detecting the differential expression, relative to a normal cell, of at least one polypeptide encoded by a nucleic acid which hybridizes under stringent conditions to a sequence selected from the group consisting of SEQ ID Nos. 4472, 4474, 4476, 4478, 4480, 4482, 4484, 4486, 4488, 4490, 4492, and 4494, wherein the polypeptide is differentially expressed by at least a factor of two.

A method of determining the phenotype of cell, comprising detecting the differential expression, relative to a normal cell, of at least one polypeptide selected from the group of polypeptides of SEQ ID Nos. 4471, 4473, 4475, 4477, 4479, 4481, 4483, 4485, 4487, 4489, 4491, and 4493, wherein the polypeptide is differentially expressed by at least a factor of two.

A method for detecting a mutation in a test nucleic acid which hybridizes under stringent conditions to a nucleic acid of SEQ ID Nos. 1-4470 or a sequence complementary thereto, comprising

(a) collecting a sample of cells from a patient,
(b) isolating nucleic acid from the cells of the sample,
(c) contacting the nucleic acid sample with one or more primers which specifically hybridize to a nucleic acid sequence of SEQ ID Nos. 1-4470 under conditions such that hybridization and amplification of the nucleic acid occurs, and
(d) comparing the presence, absence, or size of an amplification product to the amplification product of a normal cell.

1 more element

A method for identifying an agent which alters the level of expression in a cell of a nucleic acid which hybridizes under stringent conditions to one of SEQ ID Nos. 1-4470 or a sequence complementary thereto, comprising

(a) providing a cell;
(b) treating the cell with a test agent;
(c) determining the level of expression in the cell of a nucleic acid which hybridizes under stringent conditions to one of SEQ ID Nos. 1-4470 or a sequence complementary thereto;
and
(d) comparing the level of expression of the nucleic acid in the treated cell with the level of expression of the nucleic acid in an untreated cell, wherein a change in the level of expression of the nucleic acid in the treated cell relative to the level of expression of the nucleic acid in the untreated cell is indicative of an agent which alters the level of expression of the nucleic acid in a cell.

2 more elements

A method for identifying an agent which alters the level of expression in a cell of a nucleic acid which hybridizes under stringent conditions to one of SEQ ID Nos. 4472, 4474, 4476, 4478, 4480, 4482, 4484, 4486, 4488, 4490, 4492, or 4494 or a sequence complementary thereto, comprising

(a) providing a cell;
(b) treating the cell with a test agent;
(c) determining the level of expression in the cell of a nucleic acid which hybridizes under stringent conditions to one of SEQ ID Nos. 4472, 4474, 4476, 4478, 4480, 4482, 4484, 4486, 4488, 4490, 4492, or 4494 or a sequence complementary thereto;
and
(d) comparing the level of expression of the nucleic acid in the treated cell with the level of expression of the nucleic acid in an untreated cell, wherein a change in the level of expression of the nucleic acid in the treated cell relative to the level of expression of the nucleic acid in the untreated cell is indicative of an agent which alters the level of expression of the nucleic acid in a cell.

2 more elements

A method for identifying an agent which alters the level of expression in a cell of a polypeptide of one or more of SEQ ID Nos. 4471, 4473, 4475, 4477, 4479, 4481, 4483, 4485, 4487, 4489, 4491, or 4493 comprising

(a) providing a cell;
(b) treating the cell with a test agent;
(c) determining the level of expression of one or more polypeptides of SEQ ID Nos. 4471, 4473, 4475, 4477, 4479, 4481, 4483, 4485, 4487, 4489, 4491, or 4493 in said cell by reacting said cell with an antibody specific for one or more of the polypeptides of SEQ ID Nos. 4471, 4473, 4475, 4477, 4479, 4481, 4483, 4485, 4487, 4489, 4491, or 4493;
and
(d) comparing the level of expression of said one or more polypeptides in the treated cell with the level of expression of said one or more polypeptides in an untreated cell, wherein a change in the level of expression of the nucleic acid in the treated cell relative to the level of expression of the nucleic acid in the untreated cell is indicative of an agent which alters the level of expression of the polypeptide in a cell.

2 more elements

A pharmaceutical composition comprising a nucleic acid which includes a nucleotide sequence which hybridizes under stringent conditions to one of SEQ ID Nos. 1-4470 or a sequence complementary thereto.

A pharmaceutical composition comprising a polypeptide encoded by a nucleic acid which includes a nucleotide sequence that hybridizes under stringent conditions to one of SEQ ID Nos. 1-4470 or a sequence complementary thereto.

A pharmaceutical composition comprising a polypeptide having the sequence of one of SEQ ID Nos. 4471, 4473, 4475, 4477, 4479, 4481, 4483, 4485, 4487, 4489, 4491, or 4493.

A pharmaceutical composition comprising an antibody which binds to one or more polypeptides having the sequence of SEQ ID Nos. 4471, 4473, 4475, 4477, 4479, 4481, 4483, 4485, 4487, 4489, 4491, or 4493.

An isolated nucleic acid comprising a portion of a nucleotide sequence of SEQ ID Nos. 504-1103 or a sequence complementary thereto.

A gene which hybridizes to one of SEQ ID Nos. 1-503.

A method for detecting cancer in which one or more of SEQ ID Nos. 1-4470, 4472, 4474, 4476, 4478, 4480, 4482, 4484, 4486, 4488, 4490, 4492, and 4494 are used as probes, said method comprising:

(a) collecting a sample of cells from a patient,
(b) isolating nucleic acid from the cells of the sample,
(c) contacting the nucleic acid sample with one or more primers which specifically hybridize to a nucleic acid sequence of SEQ ID Nos. 1-4470, 4472, 4474, 4476, 4478, 4480, 4482, 4484, 4486, 4488, 4490, 4492, and 4494 under conditions such that hybridization and amplification of the nucleic acid occurs, and
(d) comparing the presence, absence, or size of an amplification product to the amplification product of a normal cell.

1 more element

A method for detecting cancer in a patient sample in which an antibody to a protein encoded by SEQ ID Nos. 1-4470 is used to react with proteins in said sample.

A method for detecting cancer in a patient sample in which an antibody to a protein encoded by one or more of SEQ ID Nos. 4472, 4474, 4476, 4478, 4480, 4482, 4484, 4486, 4488, 4490, 4492, or 4494 is used to react with proteins in said sample.

A method for detecting cancer in a patient sample in which an antibody to a protein having the sequence of SEQ ID Nos. 4471, 4473, 4475, 4477, 4479, 4481, 4483, 4485, 4487, 4489, 4491, or 4493 is used to react with proteins in said sample.

Dependencies are inferred from the claim text.

Nucleic acid sequences differentially expressed in cancer tissue

Life of this patent

Nucleic acid sequences differentially expressed in cancer tissue

Life of this patent

Abstract

Claims42