Human transcriptomes
AssigneeThe Johns Hopkins University
InventorsVictor E. Velculescu, Bert Vogelstein, Kenneth W. Kinzler
Life of this patent
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Abstract
Global gene expression patterns have been characterized in normal and cancerous human cells using serial analysis of gene expression (SAGE). Cancer cell-specific, cell-type specific, and ubiquitously expressed genes have been identified. This information can be used to provide combinations of cell type- and cancer-specific gene probes, as well as methods of using these probes to identify particular cell types, screen for useful drugs, reduce cancer-specific gene expression, standardize gene expression, and restore function to a diseased cell or tissue.
Claims9
A method of identifying a cell as either a colon epithelial cell, a brain cell, a keratinocyte, a breast epithelial cell, a lung epithelial cell, a melanocyte, a prostate cell, or a kidney epithelial cell, comprising the step of:
- determining expression in a test cell of a gene product of at least one gene comprising a sequence selected from at least one of the following groups:
- (a) the sequences shown in SEQ ID NOS:2, 5-18, 20-84, and 85;
- (b) the sequences shown in SEQ ID NOS:87-96, 98, 100-103, 105, 107-110, 112-129, and 131-150, and 151;
- (c) the sequences shown in SEQ ID NOS:152-154, and 155;
- (d) the sequences shown in SEQ ID NOS:156-159, and 160;
- (e) the sequences shown in SEQ ID NOS:161-166, and 167;
- (f) the sequences shown in SEQ ID NOS:168, 170, 172-177, 179-188, 190-207, and 208;
- (g) the sequences shown in SEQ ID NOS:209 and 210;
- and
- (h) the sequences shown in SEQ ID NOS:211-224 and 225,
- wherein expression of a gene product of at least one gene comprising a sequence shown in (a) identifies the test cell as a colon epithelial cell;
- wherein expression of a gene product of at least one gene comprising a sequence shown in (b) identifies the test cell as a brain cell;
- wherein expression of a gene product of at least one gene comprising a sequence shown in (c) identifies the test cell as a keratinocyte;
- wherein expression of a gene product of at least one gene comprising a sequence shown in (d) identifies the test cell as a breast epithelial cell;
- wherein expression of a gene product of at least one gene comprising a sequence shown in (e) identifies the test cell as a lung epithelial cell;
- wherein expression of a gene product of at least one gene comprising a sequence shown in (f) identifies the test cell as a melanocyte;
- wherein expression of a gene product of at least one gene comprising a sequence shown in (g) identifies the test cell as a prostate cell;
- and
- wherein expression of a gene product of at least one gene comprising a sequence shown in (h) identifies the test cell as a kidney epithelial cell.
An isolated polynucleotide comprising a sequence selected from the group consisting of SEQ ID NOS:2, 5, 6, 8, 10, 12, 13, 15, 17, 18, 21, 24-26, 28, 30, 31, 34-36, 38, 40, 47-51, 53-57, 59-62, 65-69, 71-76, 78, 80-84, 98, 103, 113, 115, 122, 129, 132, 134, 135, 140, 144, 149, 150, 153-168, 174-176, 182, 185, 186, 188, 190, 200, 201, 205-213, 216-224, 237, 239, 257, 263, 485, 487, 495, 499, 514, 586, 686, 751, 835, 844, 878, 910, 925, 932, 951, 1000, 1005, 1070, 1122, 1130, 1170, 1173, 1187, 1189, 1200, 1213, 1220, 1237, 1257, 1264, 1273, 1293, 1300, 1320, 1367, 1371, 1401, 1403, 1404, 1406, 1418, and 1419.
A method of identifying a test cell as a cancer cell, comprising the step of:
- determining expression in a test cell of a gene product of at least one gene comprising a sequence selected from the group consisting of SEQ ID NOS:228, 230-257, 259-260, and 262-265, wherein an increase in said expression of at least two-fold relative to expression of the at least one gene in a normal cell identifies the test cell as a cancer cell.
A method of reducing expression of a cancer-specific gene in a human cell, comprising the step of:
- administering to the cell a reagent which specifically binds to an expression product of a cancer-specific gene comprising a sequence selected from the group consisting of SEQ ID NOS:228, 230-257, 259-260, and 262-265, whereby expression of the cancer-specific gene is reduced relative to expression of the cancer-specific gene in the absence of the reagent.
A method for comparing expression of a gene in a test sample to expression of a gene in a standard sample, comprising the steps of:
- determining a first ratio and a second ratio, wherein the first ratio is an amount of an expression product of a test gene in a test sample to an amount of an expression product of at least one gene comprising a sequence selected from the group consisting of SEQ ID NOS:266-375, 377-652, 654-796, and 798-1448 in the test sample, and wherein the second ratio is an amount of an expression product of the test gene in a standard sample to an amount of an expression product of the at least one gene in the standard sample;
- and
- comparing the first and second ratios, wherein a difference between the first and second ratios indicates a difference in the amount of the expression product of the test gene in the test sample.
A method of screening candidate anti-cancer drugs, comprising the steps of:
- contacting a cancer cell with a test compound;
- and
- measuring expression in the cancer cell of a gene product of at least one gene comprising a sequence selected from the group consisting of SEQ ID NOS:
- 228, 230-257, 259, 260, 262-263, and 265, wherein a decrease in expression of the gene product in the presence of a test compound relative to expression of the gene product in the absence of the test compound identifies the test compound as a potential anti-cancer drug.
A method of screening test compounds for the ability to increase an organ or cell function, comprising the step of:
- contacting a cell selected from the group consisting of a colon epithelial cell, a brain cell, a keratinocyte, a breast epithelial cell, a lung epithelial cell, a melanocyte, a prostate cell, and a kidney cell with a test compound;
- and
- measuring expression in the cell of a gene product of at least one gene comprising a sequence selected from at least one of the following groups:
- (a) the sequences shown in SEQ ID NOS:2, 5-18, 20-84, and 85;
- (b) the sequences shown in SEQ ID NOS:87-96, 98, 100-103, 105, 107-110, 112-129, 131-150, and 151;
- (c) the sequences shown in SEQ ID NOS:152-154, and 155;
- (d) the sequences shown in SEQ ID NOS:156-159 and 160;
- (e) the sequences shown in SEQ ID NOS:161-166 and 167;
- (f) the sequences shown in SEQ ID NOS:168, 170, 172-177, 179-188, 190-207, and 208;
- (g) the sequences shown in SEQ ID NOS:209 and 210;
- and
- (h) the sequences shown in SEQ ID NOS:211-224 and 225,
- wherein an increase in expression of a gene product of at least one gene comprising a sequence selected from (a) identifies the test compound as a potential drug for increasing a function of a colon cell;
- wherein an increase in expression of a gene product of at least one gene comprising a sequence selected from (b) identifies the test compound as a potential drug for increasing a function of a brain cell;
- wherein an increase in expression of a gene product of at least one gene comprising a sequence selected from (c) identifies the test compound as a potential drug for increasing a function of a skin cell;
- wherein an increase in expression of a gene product of at least one gene comprising a sequence selected from (d) identifies the test compound as a potential drug for increasing a function of a breast cell;
- wherein an increase in expression of a gene product of at least one gene comprising a sequence selected from (e) identifies the test compound as a potential drug for increasing a function of a lung cell;
- wherein an increase in expression of a gene product of at least one gene comprising a sequence selected from (f) identifies the test compound as a potential drug for increasing a function of a melanocyte;
- wherein an increase in expression of a gene product of at least one gene comprising a sequence selected from (g) identifies the test compound as a potential drug for increasing a function of a prostate cell;
- and
- wherein an increase in expression of a gene product of at least one gene comprising a sequence selected from (h) identifies the test compound as a potential drug for increasing a function of a kidney cell.
A method to restore function to a diseased tissue or cell comprising the step of:
- delivering a gene to a diseased cell selected from the group consisting of a colon epithelial cell, a brain cell, a keratinocyte, a breast epithelial cell, a lung epithelial cell, a melanocyte, a prostate cell, and a kidney cell, wherein the gene comprises a nucleotide sequence selected from at least one of the following groups:
- (a) the sequences shown in SEQ ID NOS:2, 5-18, 20-84, and 85;
- (b) the sequences shown in SEQ ID NOS:87-96, 98, 100-103, 105, 107-110, 112-129, 131-150, and 151;
- (c) the sequences shown in SEQ ID NOS:152-154, and 155;
- (d) the sequences shown in SEQ ID NOS:156-159 and 160;
- (e) the sequences shown in SEQ ID NOS:161-166 and 167;
- (f) the sequences shown in SEQ ID NOS:168, 170, 172-177, 179-188, 190-207, and 208;
- (g) the sequences shown in SEQ ID NOS:209 and 210;
- and
- (h) the sequences shown in SEQ ID NOS:211-224 and 225,
- wherein expression of the gene in the diseased cell is less than expression of the gene in a corresponding cell which is normal,
- wherein if the diseased cell is a colon epithelial cell, then the nucleotide sequence is selected from (a);
- wherein if the diseased cell is a brain cell, then the nucleotide sequence is selected from (b);
- wherein if the diseased cell is a keratinocyte, then the nucleotide sequence is selected from (c);
- wherein if the diseased cell is a breast epithelial cell, then the nucleotide sequence is selected from (d);
- wherein if the diseased cell is a lung epithelial cell, then the nucleotide sequence is selected from (e);
- wherein if the diseased cell is a melanocyte, then the nucleotide sequence is selected from (f);
- wherein if the diseased cell is a prostate cell, then the nucleotide sequence is selected from (g);
- and
- wherein if the diseased cell is a kidney cell, then the nucleotide sequence is selected from (h).
Dependencies are inferred from the claim text.