Method to Predict Responsiveness of Breast Cancer to Polyamine-Type Chemotherapy

• US 20110183336A1
• Filed: 04/26/2010
• Published: 07/28/2011
• Est. Priority Date: 10/26/2007
• Status: Abandoned Application

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: CHIN, KOEI, NEVE, RICHARD M., SPELLMAN, PAUL T., GRAY, JOE W., HU, ZHI, FRIDLYAND, JANE, DAS, DEBOPRIYA, KUO, WEN-LIN, WANG, NICHOLAS J.
• Application Number:
  US12/767,725
• Publication Number:
  US 20110183336A1
• Time in Patent Office: Days
• US Class Current: 435/6.12
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: C12Q 2600/178 miRNA, siRNA or ncRNA

Abstract

Methods of-identifying a basal or luminal phenotype of a cell, comprising detecting expression of one or more of a set of predictive biomarker genes or proteins that identify the cell as having a basal or luminal cancer subtype and compositions for treating identified basal or luminal cancers.

Claims

1-13. -13. (canceled)

14. A method for identifying a basal-type cancer patient, comprising:

(a) measuring expression level of one gene selected from the group consisting of genes encoding SCNN1A, CA12, PRKX, TFF3, HNF3A, MYB, GABRP, ESR1, AGR2, GATA3, FOXC1, and EN1, in a sample from the patient; and

(b) comparing the expression level of the gene from the patient with expression level of the gene in a normal tissue sample or a reference expression level, wherein an increase of expression of one gene selected from the group consisting of the genes encoding PRKX, GABRP, FOXC1, and EN1 and a decrease of expression of one gene selected from the group consisting of the genes encoding SCNN1A, CA12, TFF3, HNF3A, MYB, ESR1, AGR2, and GATA3 indicates the patient has basal-type cancer.

15. The method of claim 14, wherein a decrease of expression of one gene selected from the group consisting of the genes encoding PRKX, GABRP, FOXC1, and EN1 and an increase of expression of one gene selected from the group consisting of the genes encoding SCNN1A, CA12, TFF3, HNF3A, MYB, ESR1, AGR2, and GATA3 indicates the patient does not have basal-type cancer.

16. The method of claim 15, further comprising (c) measuring expression level of at least two genes selected from the group consisting of SCNN1A, CA12, PRKX, TFF3, HNF3A, MYB, GABRP, ESR1, AGR2, GATA3, FOXC1, and EN1, in a sample from the patient, and (d) comparing the expression level of step (c) with expression levels of the genes in a normal tissue sample or a reference expression level, or an average expression level in a panel of normal cell lines or cancer cell lines.

17. The method of claim 16, further comprising (d) measuring the expression level of each gene in the group consisting of SCNN1A, CA12, PRKX, TFF3, HNF3A, MYB, GABRP, ESR1, AGR2, GATA3, FOXC1, and EN1 in a sample from the patient;

and (e) comparing the expression level of step (d) with expression levels of the genes in a normal tissue sample or a reference expression level, or a average expression level in a panel of normal cell lines or cancer cell lines.

18. A method for identifying a basal or luminal phenotype of a cell, comprising:

(a) measuring expression level of one gene selected from the group consisting of genes encoding SCNN1A, CA12, PRKX, TFF3, HNF3A, MYB, GABRP, ESR1, AGR2, GATA3, FOXC1, and EN1, in a patient sample; and

(b) comparing the expression level of gene from a sample with expression level of the gene in a normal tissue sample or a reference expression level, wherein an increase of expression in the patient sample of one gene selected from the group consisting of the genes encoding PRKX, GABRP, FOXC1, and EN1, indicates the cell has a basal phenotype and an increase of expression of one gene selected from the group consisting of the genes encoding SCNN1A, CA12, TFF3, HNF3A, MYB, ESR1, AGR2, and GATA3, indicates the cell has a luminal phenotype.

19. The method of claim 18, wherein a decrease of expression in the patient sample of one gene selected from the group consisting of the genes encoding PRKX, GABRP, FOXC1, and EN1, indicates the cell has a luminal phenotype, and a decrease of expression of one gene selected from the group consisting of the genes encoding SCNN1A, CA12, TFF3, HNF3A, MYB, ESR1, AGR2, and GATA3, indicates the cell has a basal phenotype.

20-32. -32. (canceled)

33. An assay to detect modulated expression of a gene as a predictor or marker of basal-type cancers, the assay comprising:

RT-PCR primers dimensioned and configured to detect transcription level of one or more genes selected from the group consisting of SCNN1A, CA12, PRKX, TFF3, HNF3A, MYB, GABRP, ESR1, AGR2, GATA3, FOXC1, and EN1.

34. An assay to detect modulated expression of a gene as a predictor or marker of basal-type cancers, the assay comprising immunochemical reagents to detect a polypeptide expressed by one or more genes selected from the group consisting of SCNN1A, CA12, PRKX, TFF3, HNF3A, MYB, GABRP, ESR1, AGR2, GATA3, FOXC1, and EN1.

35. A compound to treat a cell that exhibits modulated expression of a gene that is a predictor or maker of basal-type cancer, wherein the compound is configured to inhibit expression of one or more genes selected from the group consisting of SCNN1A, CA12, PRKX, TFF3, HNF3A, MYB, GABRP, ESR1, AGR2, GATA3, FOXC1, and EN1.

36. The compound of claim 35 to treat a cell that exhibits modulated expression of a gene that is a predictor or maker of basal-type cancer, wherein the compound comprises an siRNA or an antisense oligonucleotide.

37. The compound of claim 36 wherein the inhibitor is encoded on a viral vector that is dimensioned and configured to produce the antisense oligonucleotide or siRNA.

38. The compound of claim 35 to treat a cell that exhibits modulated expression of a gene that is a predictor or maker of basal-type cancer, wherein the compound comprising an aptamer.

39. The compound of claim 35 to treat a cell that exhibits modulated expression of a gene that is a predictor or maker of basal-type cancer, wherein the compound comprising an antibody.

40-41. -41. (canceled)