NOVEL METHODS FOR FUNCTIONAL ANALYSIS OF HIGH-THROUGHPUT EXPERIMENTAL DATA AND GENE GROUPS IDENTIFIED THEREFROM

• US 20100216660A1
• Filed: 12/19/2007
• Published: 08/26/2010
• Est. Priority Date: 12/19/2006
• Status: Active Grant

• Current Assignee: Camelot UK Bidco Limited (Clarivate Plc)
• Original Assignee: Camelot UK Bidco Limited (Clarivate Plc)
• Inventors: Bugrim, Andrej, Nikolsky, Yuri, Nikolskaya, Tatiana
• Granted Patent: US 9,353,415 B2
• Time in Patent Office: Days
• US Class Current: 506/9
• CPC Class Codes: C12P 19/34 Polynucleotides, e.g. nucleic acids, oligoribonucleotides
• CPC Class Codes: C12Q 1/68 involving nucleic acids
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G16B 5/00 ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks

Abstract

The present invention relates generally to groups of genes that can be used to diagnose and differentiate between types of specific diseases such as breast cancer. The groups of genes can be further used to develop diagnostic kits for the specific diseases. The diagnostic kits can also differentiate between sub-categories of a disease to help identify the appropriate treatment regimen for a patient.

Claims

1-27. -27. (canceled)

28. An article of manufacture for categorizing a breast cancer tissue sample, said article of manufacture comprising a means for measuring gene expression in the following descriptor groups:

(1) PSMD3, TCAP, ERBB2, THRAP4, GRB7, CRK7, GSDML, LENEP, PPARBP;

(2) DNALI1, XBP1, AR, FOXA1;

(3) GATA3, TFF3, ACADSB, ESR1, CA12;

(4) KRT17, SERPINB5, KRT5, GABRP, ANXA8, TRIM29, S100A2;

(5) KRT18, KRT8, PPP2CA, KRT8L2;

(6) COL11A1, WNT2, MMP14, PLAU, PLAUR;

(7) FN1, THY1, BAPX1, COL5A2;

(8) PSMB9, STAT1, PDCD1LG2, GBP1, CXCL10, UBE2L6, TAP1, LAP3; and

(9) CEACAM3, CEACAM5, CEACAM 6, CEACAM7.

wherein overexpression of a majority of genes in a descriptor group indicates that the tissue sample is positive for that group, and a lack of overexpression of a majority of genes in a descriptor group indicates that the tissue sample is negative for that group; and

wherein a combination of the positive and/or negative statuses for the descriptor groups forms a gene signature that is used to categorize the breast cancer tissue sample.

29. The article of manufacture of claim 28, wherein the means for measuring gene expression comprises oligonucleotide probes or primers complementary to each of the genes.

30. The article of manufacture of claim 29, wherein the complementary oligonucleotide probes are immobilized on a solid support.

31. The article of manufacture of claim 30, wherein the immobilized complementary oligonucleotide probes form an oligonucleotide array.

32. The article of manufacture of claim 29, wherein the complementary oligonucleotide primers are suitable for a reverse transcription polymerase chain reaction (RT-PCR).

33. The article of manufacture of claim 41, wherein the RT-PCR primers comprise oligonucleotides of SEQ ID NOs:

1-100;

34. A method for categorizing a breast cancer tissue sample, said method comprising:

a) measuring gene expression of the tissue sample in the descriptor groups of claim 28;

b) assigning a positive or negative status for each of the descriptor groups based on whether a majority of genes in a group are overexpressed; and

c) using a combination of the positive and/or negative statuses for the descriptor groups to form a gene signature for categorizing the breast cancer tissue sample.

35. The method of claim 34, wherein step a) comprises a nucleotide hydridization or amplification reaction.

36. The method of claim 35, wherein the nucleotide hybridization reaction is carried out on a solid support.

37. The method of claim 36, wherein the nucleotide hybridization reaction is carried out on an oligonucleotide array.

38. The method of claim 35, wherein the nucleotide amplification reaction is a reverse transcription polymerase chain reaction (RT-PCR).

39. The method of claim 38, wherein the RT-PCR is carried out using oligonucleotide primers of SEQ ID NOs:

1-100.

40. A method for assessing invasiveness of a breast cancer, said method comprising:

a) obtaining a breast cancer tissue sample from a breast cancer patient;

b) categorizing the tissue sample using the method of claim 34;

c) assessing invasiveness of the breast cancer based on the outcome of step b).

41. A method for assessing a clinical prognosis of a breast cancer patient, said method comprising:

a) obtaining a breast cancer tissue sample from the patient;

b) categorizing the tissue sample using the method of claim 34;

c) assessing a clinical prognosis of the breast cancer patient based on the outcome of step

b).

42. A method for determining a course of treatment for a breast cancer patient, said method comprising:

a) obtaining a breast cancer tissue sample from the patient;

b) categorizing the tissue sample using the method of claim 34;

c) determining a course of treatment for the breast cancer patient based on the outcome of step b).

43. An article of manufacture for categorizing a breast cancer tissue sample, said article of manufacture comprising a means for measuring gene expression in the following descriptor groups:

(1) PSMD3, TCAP, ERBB2, GRB7, THRAP4, CRK7, GSDML, LENEP, STARD3, PPARBP;

(2) DNALI1, XBP1, FOXA1, AR, ESR1, CA12, GATA3, TFF3, ACADSB;

(3) ANXA8, SERPINB5, TRIM29, S100A2, KRT17, KRT5, GABRP;

(4) KRT8L2, KRT18, KRT8, PPP2CA;

(5) COL11A1, PLAU, PLAUR, WNT2, MMP14, FN1, BAPX1, COL5A2, FAP, THY1;

(6) PSMB9, STAT1, PDCD1LG2, GBP1, CXCL10, UBE2L6, TAP1, LAP3; and

(7) CEACAM3, CEACAM5, CEACAM6, CEACAM7,

wherein overexpression of a majority of genes in a descriptor group indicates that the tissue sample is positive for that group, and a lack of overexpression of a majority of genes in a descriptor group indicates that the tissue sample is negative for that group; and

wherein a combination of the positive and/or negative statuses for the descriptor groups forms a gene signature that is used to categorize the breast cancer tissue sample.

44. A method for categorizing a breast cancer tissue sample, said method comprising:

a) measuring gene expression of the tissue sample in the descriptor groups of claim 43;

b) assigning a positive or negative status for each of the descriptor groups based on whether a majority of genes in a group are overexpressed; and

c) using a combination of the positive and/or negative statuses for the descriptor groups to form a gene signature for categorizing the breast cancer tissue sample.

45. An article of manufacture for categorizing a breast cancer tissue sample, said article of manufacture comprising a means for measuring gene expression in the following descriptor groups:

(1) ERBB2, STARD3, GRB7, THRAP4, PPARBP;

(2) ESR1, GATA3, XBP1, TFF3, ACADSB;

(3) KRT5, KRT17, TRIM29, GABRP;

(4) KRT18, KRT8, PPP2CA, KRT8L2;

(5) PLAU, COL5A2, FAP, THY1;

(6) STAT1, UBE2L6, TAP1, LAP3; and

(7) SEACAM5, SEACAM6, SEACAM7,

wherein overexpression of a majority of genes in a descriptor group indicates that the tissue sample is positive for that group, and a lack of overexpression of a majority of genes in a descriptor group indicates that the tissue sample is negative for that group; and

wherein a combination of the positive and/or negative statuses for the descriptor groups forms a gene signature that is used to categorize the breast cancer tissue sample.

46. A method for categorizing a breast cancer tissue sample, said method comprising:

a) measuring gene expression of the tissue sample in the descriptor groups of claim 45;

b) assigning a positive or negative status for each of the descriptor groups based on whether a majority of genes in a group are overexpressed; and

c) using a combination of the positive and/or negative statuses for the descriptor groups to form a gene signature for categorizing the breast cancer tissue sample.