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 distinguishing melanoma from dysplastic nevi or normal pigmented skin in a human subject comprising:
 (a) obtaining a sample of a skin lesion from a human subject;   (b) analyzing expression of a nucleic acid molecule encoding a protein selected from among:   
       endothelin receptor type B; Hypothetical protein MGC40222; tetratricopeptide repeat domain 3; staufen, RNA binding protein (Drosophila); actinin, alpha 4; KIAA1212; glycoprotein M6B; v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog; c-Maf-inducing protein; adaptor-related protein complex 2, mu 1 subunit; syntaxin 5A; chemokine-like factor superfamily 4; UDP-Gal: betaGlcNAc beta 1,4-galactosyl-transferase, polypeptide 5; fibrosin 1; ortholog of mouse neighbor of Punc E11; myosin, heavy polypeptide 14; preferentially expressed antigen in melanoma; jumonji domain containing 3; BCL2-related protein A1; formin binding protein 1, and combinations thereof, in the sample; and
 (c) characterizing the skin lesion as being melanoma, dysplastic nevi, or normal pigmented skin, thereby distinguishing melanoma from dysplastic nevi or normal pigmented skin in a human subject. 
 
     
     
         2 . The method of  claim 1 , wherein the nucleic acid molecule is RNA. 
     
     
         3 . The method of  claim 1 , further comprising amplifying the nucleic acid molecule prior to analyzing. 
     
     
         4 . The method of  claim 1 , wherein the nucleic acid molecule or an amplification product thereof, is applied to a microarray. 
     
     
         5 . The method of  claim 4 , wherein an expression profile is detected using the microarray. 
     
     
         6 . The method of  claim 1 , wherein the sample is obtained by applying an adhesive tape to a target area of skin in a manner sufficient to isolate the sample adhering to the adhesive tape. 
     
     
         7 . The method of  claim 1 , wherein the sample is obtained from a biopsy taken at the site of the skin lesion. 
     
     
         8 . The method of  claim 6 , wherein the tape comprises a rubber adhesive on a polyurethane film. 
     
     
         9 . The method of  claim 6 , wherein about one to ten adhesive tapes or one to ten applications of a tape are applied and removed from the skin. 
     
     
         10 . The method of  claim 6 , wherein about one to eight adhesive tapes or one to eight applications of a tape are applied and removed from the skin. 
     
     
         11 . The method of  claim 6 , wherein about one to five adhesive tapes or one to five applications of a tape are applied and removed from the skin. 
     
     
         12 . The method of  claim 6 , wherein the method further comprises taking a biopsy of the target area of the skin. 
     
     
         13 . The method of  claim 1 , wherein the analyzing is performed in situ. 
     
     
         14 . The method of  claim 1 , further comprising determining a treatment regimen. 
     
     
         15 . A method for diagnosing melanoma in a subject, comprising:
 (a) providing a gene expression profile of a target area suspected of being melanoma on the skin of the subject, wherein the target area of the skin simultaneously expresses a plurality of genes at the protein level that are markers for melanoma; and   (b) analyzing the subject's gene expression profile to a reference gene expression profile obtained from a corresponding normal skin sample, wherein the reference gene expression profile comprises an expression value of a target gene that encodes a protein selected from the group consisting of:   endothelin receptor type B; Hypothetical protein MGC40222; tetratricopeptide repeat domain 3; staufen, RNA binding protein (Drosophila); actinin, alpha 4; KIAA1212; glycoprotein M6B; v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog; c-Maf-inducing protein; adaptor-related protein complex 2, mu 1 subunit; syntaxin 5A; chemokine-like factor superfamily 4; UDP-Gal: betaGlcNAc beta 1,4-galactosyl-transferase, polypeptide 5; fibrosin 1; ortholog of mouse neighbor of Punc E11; myosin, heavy polypeptide 14; preferentially expressed antigen in melanoma; jumonji domain containing 3; BCL2-related protein A1; formin binding protein 1; or any combination thereof.   
     
     
         16 . The method of  claim 15 , wherein the reference gene expression profile further comprises an expression value of an additional target gene listed in Tables 1-7. 
     
     
         17 . The method of  claim 15 , wherein the reference gene expression profile is contained with a database. 
     
     
         18 . The method of  claim 15 , wherein the analyzing step is carried out using a computer. 
     
     
         19 . A kit for characterizing a skin lesion in a subject comprising a skin sample collection device and one or more probes or primers that selectively bind to a nucleic acid molecule encoding a protein selected from among:
 endothelin receptor type B; Hypothetical protein MGC40222; tetratricopeptide repeat domain 3; staufen, RNA binding protein (Drosophila); actinin, alpha 4; KIAA1212; glycoprotein M6B; v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog; c-Maf-inducing protein; adaptor-related protein complex 2, mu 1 subunit; syntaxin 5A; chemokine-like factor superfamily 4; UDP-Gal: betaGlcNAc beta 1,4-galactosyl-transferase, polypeptide 5; fibrosin 1; ortholog of mouse neighbor of Punc E11; myosin, heavy polypeptide 14; preferentially expressed antigen in melanoma; jumonji domain containing 3; BCL2-related protein A1; and formin binding protein 1.   
     
     
         20 . The kit of  claim 19 , wherein the skin sample collection device is an adhesive tape.