Genes and gene signatures for diagnosis and treatment of melanoma

1. A method for treating melanoma in a patient in need thereof, the method comprising:

measuring in a sample taken from a site on the patient mRNA expression of a panel of genes normalized to one or more housekeeping genes, the panel of genes comprising:

PRAME, S100A7, S100A8, S100A9, S100A12, PI3, CCL5, CD38, CXCL10, CXCL9, IRF1, LCP2, PTPRC, and SELL;

calculating a combined score of the measured mRNA expression of each of the panel of genes;

classifying the sample as being a malignancy based on the combined score exceeding a reference value; and

administering to the patient having the malignancy a treatment comprising one or more of:

excising the malignancy;

reexcising the site of the sample to remove additional tissue;

lymph node dissection;

radiation therapy;

chemotherapy;

biological therapy;

immunotherapy;

targeted therapy; and

a melanoma drug.

2. The method of claim 1 , wherein

excising the malignancy comprises excising a border of normal skin and/or a layer of tissue beneath the malignancy;

biological therapy comprises administering one or more of interferon, interleukin-2, and ipilimumab;

immunotherapy comprises administering one or more of interferon-alpha, anti-CTLA-4, a vaccine, a Bacille Calmette-Guerin vaccine, interleukin 2, and T-cell therapy;

targeted therapy comprises administering one or more of vemurafenib, a BRAF inhibitor, and a KIT inhibitor; and

a melanoma drug comprises one or more drugs selected from aldesleukin, dabrafenib, dacarbazine, interferon alfa-2b, peginterferon alfa-2b, ipilimumab, trametinib, vemurafenib, a Bacille Calmette-Guerin (BCG) vaccine, interleukin-2, imiquimod, temozolomide, and a beta-adrenergic-blocker.

3. The method of claim 1 , wherein the reference value is selected using an ROC curve of expression levels of the panel of genes in malignant melanoma and benign samples from a reference population of patients, wherein the ROC curve has a sensitivity of at least 0.8.

4. The method of claim 1 , wherein the panel of genes further comprises S100A10, and S100A14.

5. The method of claim 1 , wherein the one or more housekeeping genes is selected from the group consisting of CLTC, PPP2CA, MRFAP1, PSMA1, RPL13A, TXNL1, SLC25A3, RPS29, RPL8, PSMC1, and RPL.

6. The method of claim 1 , wherein the panel of genes further comprises PTPN22.

7. The method of claim 1 , wherein the combined score is calculated by logistic regression which determines coefficients for a weighted summing of the expression of the panel of genes.

8. The method of claim 1 , wherein the expression of the panel of genes is measured by qPCR.

9. The method of claim 1 , wherein the sample is a skin lesion.

10. A method for treating melanoma in a patient, the method comprising:

measuring in a first sample from the patient mRNA expression of a panel of genes normalized to one or more housekeeping genes, the panel of genes comprising:

PRAME, S100A7, S100A8, S100A9, S100A12, PI3, CCL5, CD38, CXCL10, CXCL9, IRF1, LCP2, PTPRC, and SELL;

calculating a first combined score of the measured mRNA expression of each of the panel of genes;

classifying the sample as having a low risk of being a malignancy based on the combined score not exceeding a reference value; and

administering to the patient having a low risk of malignancy a treatment comprising a regimen of watchful waiting;

measuring in a second sample from the patient expression of the panel of genes;

calculating a second combined score from the expression of the panel of genes;

classifying the second sample as having a high risk of being a malignancy based on the second combined score exceeding a reference value; and

administering to the patient having a high risk of malignancy a treatment comprising one or more of:

excising the malignancy;

reexcising the site of the sample to remove additional tissue;

lymph node dissection;

radiation therapy;

chemotherapy;

biological therapy;

immunotherapy;

targeted therapy; and

a melanoma drug.

11. The method of claim 10 , wherein

excising the malignancy comprises excising a border of normal skin and/or a layer of tissue beneath the malignancy;

biological therapy comprises administering one or more of interferon, interleukin-2, and ipilimumab;

immunotherapy comprises administering one or more of interferon-alpha, anti-CTLA-4, a vaccine, a Bacille Calmette-Guerin vaccine, interleukin 2, and T-cell therapy;

targeted therapy comprises administering one or more of vemurafenib, a BRAF inhibitor, and a KIT inhibitor; and

a melanoma drug comprises one or more drugs selected from aldesleukin, dabrafenib, dacarbazine, interferon alfa-2b, peginterferon alfa-2b, ipilimumab, trametinib, vemurafenib, a Bacille Calmette-Guerin (BCG) vaccine, interleukin-2, imiquimod, temozolomide, and a beta-adrenergic-blocker.

12. The method of claim 10 , wherein the reference value is selected using an ROC curve of expression levels of the panel of genes in malignant melanoma and benign samples from a reference population of patients, wherein the ROC curve has a sensitivity of at least 0.8.

13. The method of claim 10 , wherein the panel of genes further comprises S100A10, and S100A14.

14. The method of claim 10 , wherein the one or more housekeeping genes is selected from the group consisting of CLTC, PPP2CA, MRFAP1, PSMA1, RPL13A, TXNL1, SLC25A3, RPS29, RPL8, PSMC1, and RPL.

15. The method of claim 10 , wherein the panel of genes further comprises PTPN22.

16. The method of claim 10 , wherein the combined score is calculated by logistic regression which determines coefficients for a weighted summing of the expression of the panel of genes.

17. The method of claim 10 , wherein the expression of the panel of genes is measured by qPCR.

18. The method of claim 10 , wherein the sample is a skin lesion.