Prognosis prediction for melanoma cancer

• US 20100136553A1
• Filed: 11/23/2009
• Published: 06/03/2010
• Est. Priority Date: 05/24/2007
• Status: Active Grant

• Current Assignee: Ludwig Institute for Cancer Research, Ltd., Pacific Edge Ltd.
• Original Assignee: Pacific Edge Ltd.
• Inventors: John, Thomas, Cebon, Jonathan, Black, Michael Alan, Guilford, Parry John
• Granted Patent: US 8,822,149 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: C12Q 2600/16 Primer sets for multiplex assays
• CPC Class Codes: G16H 50/30 for calculating health indices; for individual health risk assessment

Abstract

The invention relates to prognostic markers and prognostic signatures, and compositions and methods for determining the prognosis of cancer in a patient, particularly for melanoma. Specifically, the invention relates to the use of genetic and protein markers for the prediction of the risk of progression of a cancer, such as melanoma, based on markers and signatures of markers. In various aspects, the invention provides methods, compositions, kits, and devices based on prognostic cancer markers, specifically melanoma prognostic markers, to aid in the prognosis and treatment of cancer.

Claims

1. A prognostic signature for determining the risk of progression of melanoma, comprising two or more melanoma prognostic markers (MPMs).

2. The signature of claim 1, wherein the MPMs are selected from table 1.

3. A device for determining prognosis of melanoma, comprising:

a substrate having two or more locations thereon, each of said locations having an MPM oligonucleotide thereon.

4. The device of claim 3, wherein each of said oligonucleotides is an MPM selected from table 1.

13. The method of claim 8, wherein the step of determining the expression level of an MPM or of a prognostic signature is carried out using a device according to claim 3.

5. A method for determining the prognosis of melanoma in a patient, comprising the steps of;

(i) determining the expression level of an MPM, or of a prognostic signature comprising two or more MPMs, in a melanoma tumour sample from the patient,

(ii) applying a predictive model, established by applying a predictive method to expressions levels of the MPM or of the prognostic signature in prognostically good and poor tumour samples,

(iii) establishing a prognosis.

7. The method of claim 5, wherein the MPM or said signature is selected from the MPMs listed in table 1.

8. The method of claim 5, wherein said predictive method is selected from the group consisting of linear models, support vector machines, neural networks, classification and regression trees, ensemble learning methods, discriminant analysis, nearest neighbor method, bayesian networks, independent components analysis.

9. The method of claim 5, wherein the step of determining the expression level of said MPM or said prognostic signature is carried out by detecting the expression level of mRNA of each of said MPM genes.

10. The method of claim 5, wherein the step of determining the expression level of said MPM or of said prognostic signature is carried out by detecting the expression level of cDNA of each of said MPM genes.

11. The method of claim 10, wherein the step of determining the expression level of said MPM or of said prognostic signature is carried out using a nucleotide complementary to at least a portion of said cDNA of said MPM gene.

12. The method of claim 9, wherein the step of determining the expression level of said MPM or of said prognostic signature is carried out using a qPCR method using a forward primer and a reverse primer.

14. The method of claim 5, wherein the step of determining the expression level of said MPM or of said prognostic signature is carried out by detecting the expression level of a protein of each MPM.

15. The method of claim 5, wherein the step of determining the expression level of said MPM or of said prognostic signature is carried out by detecting the expression level of a peptide of each MPM.

16. The method of claim 15, wherein said step of detecting is carried out using an antibody directed against each MPM.

17. The method of claim 16, wherein said step of detecting is carried out using a sandwich-type immunoassay method.

18. The method of claim 16, wherein said antibody is a monoclonal antibody.

19. The method of claim 16, wherein said antibody is a polyclonal antiserum.

20. The method of claim 5, wherein said MPMs are the genes IDH, MFG8, PILRA, HLA-E and TXNDC5, and wherein expression of each of said MPMs from a sample from a patient is determined using qPCR;

and

calculating a score (“

qPS”

) according to the formula;

qPS=[1328.15−

187.42(IDH)+137.10(MFG8)+73.61(PILRA)+211.22(HLA-E)+143.94(TXNDC5)]×

−

1,

wherein a qPS score of less than zero indicates poor prognosis and a qPS score of greater than zero indicates good prognosis.

6. A method for determining the suitability of a melanoma patient for a drug trial, comprising the steps of;

(i) determining the expression level of an MPM, or of a prognostic signature comprising two or more MPMs, in a melanoma tumour sample from the patient,

(ii) applying a predictive model, established by applying a predictive method to expression levels of the MPM or of the prognostic signature in prognostically good and poor tumour samples,

(iii) establishing the suitability of the patient to the trial.