US2003198972A1PendingUtilityA1

Grading of breast cancer

Priority: Dec 21, 2001Filed: Aug 1, 2002Published: Oct 23, 2003
Est. expiryDec 21, 2021(expired)· nominal 20-yr term from priority
C12Q 1/6886A61K 31/138C12Q 2600/112C12Q 2600/16C12Q 2600/158G01N 33/57595G01N 33/57515
62
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Claims

Abstract

Methods and compositions for the identification of breast cancer grade signatures are provided. The signature profiles are identified based upon multiple sampling of reference breast tissue samples from independent cases of breast cancer and provide a reliable set of molecular criteria for identification of cells as being in one or more particular stages and/or grades of breast cancer.

Claims

exact text as granted — not AI-modified
We claim:  
     
         1 . An array comprising polynucleotide probes, capable of hybridizing to nucleic acid molecules of more than one of the genes listed in Table 2, hybridized to nucleic acids derived from a cell suspected of being non-normal.  
     
     
         2 . The array of  claim 1  comprising 3-11 of the genes.  
     
     
         3 . The array of  claim 2  comprising 5-11 of the genes.  
     
     
         4 . The array of  claim 3  comprising all 11 genes.  
     
     
         5 . The array of  claim 1  wherein said cell is from a subject afflicted with, or suspected of having, breast cancer.  
     
     
         6 . The array of  claim 1  wherein said cell is a human cell.  
     
     
         7 . The array of  claim 1  wherein said nucleic acids derived from a cell are prepared by quantitative PCR.  
     
     
         8 . The array of  claim 1  wherein at least one polynucleotide probe hybridizes to CRIP1 nucleic acid molecules.  
     
     
         9 . The array of  claim 1  wherein said non-normal cells are selected from ADH, DCIS, and IDC.  
     
     
         10 . An array comprising polynucleotide probes, capable of hybridizing to nucleic acid molecules of more than one of the genes in Table 3, hybridized to nucleic acids derived from a cell suspected of being DCIS or IDC.  
     
     
         11 . The array of  claim 10  comprising 3-9 of the genes.  
     
     
         12 . The array of  claim 11  comprising 5-9 of the genes.  
     
     
         13 . The array of  claim 12  comprising all 9 genes.  
     
     
         14 . The array of  claim 10  wherein said cell is from a subject afflicted with, or suspected of having, breast cancer.  
     
     
         15 . The array of  claim 10  wherein said cell is a human cell.  
     
     
         16 . The array of  claim 10  wherein said nucleic acids derived from a cell are prepared by quantitative PCR.  
     
     
         17 . An array comprising polynucleotide probes, capable of hybridizing to nucleic acid molecules of more than one of the genes in Table 4, hybridized to nucleic acids derived from a cell suspected of being non-normal.  
     
     
         18 . The array of  claim 17  comprising 3-9 of the genes.  
     
     
         19 . The array of  claim 18  comprising 5-9 of the genes.  
     
     
         20 . The array of  claim 19  comprising all 9 genes.  
     
     
         21 . The array of  claim 17  wherein said cell is from a subject afflicted with, or suspected of having, breast cancer.  
     
     
         22 . The array of  claim 17  wherein said cell is a human cell.  
     
     
         23 . The array of  claim 17  wherein said nucleic acids derived from a cell are prepared by quantitative PCR.  
     
     
         24 . The array of  claim 17  wherein at least one polynucleotide probe hybridizes to ELF5 nucleic acid molecules.  
     
     
         25 . The array of  claim 17  wherein said non-normal cells are selected from ADH, DCIS, and IDC  
     
     
         26 . A method to determine the presence, grade or stage of breast cancer cells in a sample from a subject comprising assaying said sample for expression of one or more genes in Table 2 and/or one or more genes in Table 4.  
     
     
         27 . The method of  claim 26  wherein said assaying comprises preparing RNA from said sample.  
     
     
         28 . The method of  claim 27  wherein said RNA is used for quantitative PCR.  
     
     
         29 . The method of  claim 28  wherein said assaying comprises using an array.  
     
     
         30 . The method of  claim 26  wherein said sample is a ductal lavage or fine needle aspiration sample.  
     
     
         31 . The method of  claim 30  wherein said sample is microdissected to isolate one or more cells suspected of being breast cancer cells.  
     
     
         32 . The method of  claim 26  wherein said non-normal cells are selected from ADH, DCIS, and IDC.  
     
     
         33 . A method to determine the presence, grade or stage of breast cancer cells in a sample from a subject comprising 
 assaying said sample for expression of one or more genes selected from Table 2 and/or Table 4 and    identifying said sample as containing non-normal breast cancer cells, optionally without grading by histomorphological criteria.    
     
     
         34 . The method of  claim 33  wherein said assaying comprises preparing RNA from said sample.  
     
     
         35 . The method of  claim 34  wherein said RNA is used for quantitative PCR.  
     
     
         36 . The method of  claim 33  wherein said assaying comprises using an array.  
     
     
         37 . The method of  claim 33  wherein said sample is a ductal lavage or fine needle aspiration sample.  
     
     
         38 . The method of  claim 37  wherein said sample is microdissected to isolate one or more cells suspected of being breast cancer cells.  
     
     
         39 . The method of  claim 33  wherein said non-normal cells are selected from ADH, DCIS, and IDC.  
     
     
         40 . A method to determine the presence of DCIS and/or IDC breast cancer cells of grade III in a sample from a subject comprising 
 assaying said sample for expression of one or more genes selected from Table 3, Table 6, and/or Table 9 and    identifying said sample as containing breast cancer cells of grade III, optionally without grading by histomorphological criteria.    
     
     
         41 . The method of  claim 40  wherein said assaying comprises preparing RNA from said sample.  
     
     
         42 . The method of  claim 41  wherein said RNA is used for quantitative PCR.  
     
     
         43 . The method of  claim 40  wherein said assaying comprises using an array.  
     
     
         44 . The method of  claim 40  wherein said sample is a ductal lavage or fine needle aspiration sample.  
     
     
         45 . The method of  claim 44  wherein said sample is microdissected to isolate one or more cells suspected of being breast cancer cells.  
     
     
         46 . A method to determine the grade of either DCIS or IDC cancer progression in a sample from a subject comprising assaying said sample for expression of one or more genes listed in Table 10.  
     
     
         47 . The method of  claim 46  wherein said assaying comprises preparing RNA from said sample.  
     
     
         48 . The method of  claim 47  wherein said RNA is used for quantitative PCR.  
     
     
         49 . The method of  claim 46  wherein said assaying comprises using an array.  
     
     
         50 . The method of  claim 49  wherein said sample is a ductal lavage or fine needle aspiration sample.  
     
     
         51 . The method of  claim 50  wherein said sample is microdissected to isolate one or more cells suspected of being breast cancer cells.  
     
     
         52 . A method to determine the presence of DCIS and/or IDC breast cancer cells of grade I in a sample from a subject comprising 
 assaying said sample for expression of one or more genes selected from Table 7 and/or Table 8 and    identifying said sample as containing breast cancer cells of grade I, optionally without grading by histomorphological criteria.    
     
     
         53 . The method of  claim 52  wherein said assaying comprises preparing RNA from said sample.  
     
     
         54 . The method of  claim 53  wherein said RNA is used for quantitative PCR.  
     
     
         55 . The method of  claim 52  wherein said assaying comprises using an array.  
     
     
         56 . The method of  claim 55  wherein said sample is a ductal lavage or fine needle aspiration sample.  
     
     
         57 . The method of  claim 56  wherein said sample is microdissected to isolate one or more cells suspected of being breast cancer cells.  
     
     
         58 . A method to determine the presence of DCIS and/or IDC breast cancer cells of grade I and/or grade III in a sample from a subject comprising assaying said sample for decreased expression of one or more genes selected from Table 5.  
     
     
         59 . The method of  claim 58  wherein said assaying comprises preparing RNA from said sample.  
     
     
         60 . The method of  claim 59  wherein said RNA is used for quantitative PCR.  
     
     
         61 . The method of  claim 58  wherein said assaying comprises using an array.  
     
     
         62 . The method of  claim 58  wherein said sample is a ductal lavage or fine needle aspiration sample.  
     
     
         63 . The method of  claim 62  wherein said sample is microdissected to isolate one or more cells suspected of being breast cancer cells.  
     
     
         64 . An array comprising polynucleotide probes, capable of hybridizing to nucleic acid molecules of more than one of the genes listed in Table 5, hybridized to nucleic acids derived from a cell suspected of being DCIS or IDC.  
     
     
         65 . The array of  claim 41  comprising 3-11 of the genes.  
     
     
         66 . The array of  claim 64  wherein said cell is from a subject afflicted with, or suspected of having, breast cancer.  
     
     
         67 . The array of  claim 64  wherein said cell is a human cell.  
     
     
         68 . The array of  claim 64  wherein said nucleic acids derived from a cell are prepared by quantitative PCR.  
     
     
         69 . An array comprising polynucleotide probes, capable of hybridizing to nucleic acid molecules of more than one of the genes listed in Table 6 and/or Table 9, hybridized to nucleic acids derived from a cell suspected of being grade III DCIS and/or IDC.  
     
     
         70 . The array of  claim 69  comprising 3-11 of the genes.  
     
     
         71 . The array of  claim 69  wherein said cell is from a subject afflicted with, or suspected of having, breast cancer.  
     
     
         72 . The array of  claim 69  wherein said cell is a human cell.  
     
     
         73 . The array of  claim 69  wherein said nucleic acids derived from a cell are prepared by quantitative PCR.  
     
     
         74 . An array comprising polynucleotide probes, capable of hybridizing to nucleic acid molecules of more than one of the genes listed in Table 7 and/or Table 8, hybridized to nucleic acids derived from a cell suspected of being grade I DCIS and/or IDC.  
     
     
         75 . The array of  claim 74  comprising 3-11 of the genes.  
     
     
         76 . The array of  claim 74  wherein said cell is from a subject afflicted with, or suspected of having, breast cancer.  
     
     
         77 . The array of  claim 74  wherein said cell is a human cell.  
     
     
         78 . The array of  claim 74  wherein said nucleic acids derived from a cell are prepared by quantitative PCR.  
     
     
         79 . An array comprising polynucleotide probes, capable of hybridizing to nucleic acid molecules of more than one of the genes listed in Table 10, hybridized to nucleic acids derived from a cell suspected of being DCIS or IDC.  
     
     
         80 . The array of  claim 79  comprising 3-11 of the genes.  
     
     
         81 . The array of  claim 79  wherein said cell is from a subject afflicted with, or suspected of having, breast cancer.  
     
     
         82 . The array of  claim 79  wherein said cell is a human cell.  
     
     
         83 . The array of  claim 79  wherein said nucleic acids derived from a cell are prepared by quantitative PCR.  
     
     
         84 . A method to determine therapeutic treatment for a patient having cells suspected of being non-normal in a sample therefrom comprising 
 identifying said patient as having grade III DCIS and/or IDC after assaying said cells for expression of more than one gene listed in Table 3 and    selecting the appropriate treatment for a patient having cells of such a grade.    
     
     
         85 . The method of  claim 84  wherein said assaying comprises preparing RNA from said cells.  
     
     
         86 . The method of  claim 85  wherein said RNA is used for quantitative PCR.  
     
     
         87 . The method of  claim 84  wherein said assaying comprises using an array.  
     
     
         88 . The method of  claim 87  wherein said sample is a ductal lavage or fine needle aspiration sample.  
     
     
         89 . The method of  claim 88  wherein said sample is microdissected to isolate one or more cells suspected of being breast cancer cells.  
     
     
         90 . The method of  claim 84  wherein said non-normal cells are selected from ADH, DCIS, and IDC.  
     
     
         91 . A method to determine therapeutic treatment for a patient having non-normal cells in a sample therefrom comprising 
 identifying said patient as having grade III DCIS and/or IDC after assaying said cells for expression of more than one gene listed in Table 6 and/or Table 9, and    selecting the appropriate treatment for a patient having cells of such a grade.    
     
     
         92 . The method of  claim 91  wherein said assaying comprises preparing RNA from said cells.  
     
     
         93 . The method of  claim 92  wherein said RNA is used for quantitative PCR.  
     
     
         94 . The method of  claim 91  wherein said assaying comprises using an array.  
     
     
         95 . The method of  claim 91  wherein said sample is a ductal lavage or fine needle aspiration sample.  
     
     
         96 . The method of  claim 95  wherein said sample is microdissected to isolate one or more cells suspected of being breast cancer cells.  
     
     
         97 . The method of  claim 91  wherein said non-normal cells are selected from ADH, DCIS, and IDC.  
     
     
         98 . A method to determine therapeutic treatment for a patient having non-normal cells in a sample therefrom comprising 
 identifying said patient as having grade I DCIS and/or IDC after assaying said cells for expression of more than one gene listed in Table 7 and/or Table 8, and    selecting the appropriate treatment for a patient having cells of such a grade.    
     
     
         99 . The method of  claim 98  wherein said assaying comprises preparing RNA from said cells.  
     
     
         100 . The method of  claim 99  wherein said RNA is used for quantitative PCR.  
     
     
         101 . The method of  claim 98  wherein said assaying comprises using an array.  
     
     
         102 . The method of  claim 98  wherein said sample is a ductal lavage or fine needle aspiration sample.  
     
     
         103 . The method of  claim 102  wherein said sample is microdissected to isolate one or more cells suspected of being breast cancer cells.  
     
     
         104 . The method of  claim 98  wherein said non-normal cells are selected from ADH, DCIS, and IDC.

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