Diagnosis of melanoma and solar lentigo by nucleic acid analysis

Abstract

The present invention provides methods for diagnosing melanoma and/or solar lentigo in a subject by analyzing nucleic acid molecules obtained from the subject. The present invention also provides methods for distinguishing melanoma from solar lentigo and/or dysplastic nevi and/or normal pigmented skin. The methods include analyzing expression or mutations in epidermal samples, of one or more skin markers. The methods can include the use of a microarray to analyze gene or protein profiles from a sample

What is claimed is: 
     
         1 . A method of detecting an expression level of one or more genes that are differentially expressed in melanoma relative to atypical nevi or normal pigmented skin, comprising:
 a) obtaining a biological sample of a skin lesion obtained with an adhesive tape, wherein the biological sample comprises or is suspected of comprising a nucleic acid expressed from one or more genes that are differentially expressed in melanoma relative to atypical nevi or normal pigmented skin; and   b) detecting the expression level of the one or more genes in the biological sample to determine whether the expression level of the one or more genes in the biological sample is at a level above an expression level of the one or more genes in an atypical nevus or normal pigmented skin sample by a hybridization assay, wherein a presence of the nucleic acid in the biological sample in an amount that is greater than in the atypical nevus or normal pigmented skin sample is indicative of melanoma in the biological sample with a sensitivity above 80%, or with a specificity of at least about 79%.   
     
     
         2 . The method of  claim 1 , wherein the presence of the nucleic acid in the biological sample in an amount that is greater than in the atypical nevus or normal pigmented skin sample is indicative of melanoma in the biological sample with a sensitivity above 80%. 
     
     
         3 . The method of  claim 1 , wherein the presence of the nucleic acid in the biological sample in an amount that is greater than in the atypical nevus or normal pigmented skin sample is indicative of melanoma in the biological sample with a sensitivity of at least 92%. 
     
     
         4 . The method of  claim 1 , wherein the presence of the nucleic acid in the biological sample in an amount that is greater than in the atypical nevus or normal pigmented skin sample is indicative of melanoma in the biological sample with a specificity of at least about 79%. 
     
     
         5 . The method of  claim 1 , wherein the presence of the nucleic acid in the biological sample in an amount that is greater than in the atypical nevus or normal pigmented skin sample is indicative of melanoma in the biological sample with a positive predictive value of at least 74%. 
     
     
         6 . The method of  claim 1 , wherein the presence of the nucleic acid in the biological sample in an amount that is greater than in the atypical nevus or normal pigmented skin sample is indicative of melanoma in the biological sample with a negative predictive value of about 100%. 
     
     
         7 . The method of  claim 1 , wherein the hybridization assay comprises application of a detectably labeled probe that hybridizes to the nucleic acid. 
     
     
         8 . The method of  claim 1 , wherein the nucleic acid comprises RNA. 
     
     
         9 . The method of  claim 8 , wherein detecting the expression level of the one or more genes in the biological sample comprises generating cDNA from the RNA. 
     
     
         10 . The method of  claim 8 , wherein the hybridization assay comprises polymerase chain reaction, microarray hybridization, or sequencing. 
     
     
         11 . The method of  claim 1 , wherein the one or more genes comprise a gene listed in any of Tables 1-8 or 10-12. 
     
     
         12 . The method of  claim 1 , wherein the one or more genes comprise preferentially expressed antigen in melanoma (PRAME) or C6orf218. 
     
     
         13 . The method of  claim 1 , wherein obtaining the biological sample comprises applying the adhesive tape to the skin lesion, thereby adhering skin cells of the skin lesion to the adhesive tape. 
     
     
         14 . The method of  claim 13 , wherein the skin cells comprise stratum corneum cells. 
     
     
         15 . The method of  claim 1 , further comprising applying a model to the expression level of the one or more genes in the biological sample to determine whether the expression level of the one or more genes in the biological sample is indicative of a melanoma, an atypical nevus, or normal pigmented skin. 
     
     
         16 . The method of  claim 15 , wherein the expression level of the one or more genes in the biological sample is indicative of a melanoma. 
     
     
         17 . The method of  claim 15 , wherein the expression level of the one or more genes in the biological sample is indicative of an atypical nevus. 
     
     
         18 . The method of  claim 15 , wherein the expression level of the one or more genes in the biological sample is indicative of normal pigmented skin. 
     
     
         19 . The method of  claim 15 , wherein the model has been trained using a Prediction Analysis of Microarrays, random forest, or TREENET analysis. 
     
     
         20 . The method of  claim 16 , further comprising providing or predicting a cancer treatment for the subject.