Gene classifiers and uses thereof in skin cancers

Abstract

Disclosed herein, in certain embodiments, are methods of detecting the presence of a skin cancer based on molecular risk factors. In some instances, the skin cancer is cutaneous T cell lymphoma (CTCL). In some cases, the skin cancer is mycosis fungoides (1VIF) or Sézary syndrome (SS).

1 . A method of analyzing a gene expression signature associated with cutaneous T cell lymphoma (CTCL) in a skin sample, comprising:
 a) isolating nucleic acids from the skin sample obtained from a subject suspected of having CTCL by applying an adhesive patch to a skin region of the subject in a manner sufficient to adhere skin sample cells to the adhesive patch, and removing the adhesive patch from the skin region in a manner sufficient to retain the adhered skin sample cells to the adhesive patch, wherein the skin sample cells comprise cells from the stratum corneum;   b) measuring expression level of a panel of target genes known to be upregulated or downregulated in subjects with CTCL compared to the expression level of equivalent target genes in a paired control skin sample;   c) using a software program or module to evaluate the gene expression levels determined in step (b) to determine the gene expression signature of the skin sample; and;   d) providing a sample score indicative of the presence or absence and/or the progression of CTCL based on the gene expression signature determined in step (c).   
     
     
         2 . The method of  claim 1 , wherein the nucleic acids comprise mRNA. 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the skin sample does not comprise melanocytes. 
     
     
         6 . The method of  claim 1 , wherein the skin sample is obtained by applying a plurality of adhesive patches to the skin region of the subject in a manner sufficient to adhere skin sample cells to each of the adhesive patches, and removing each of the plurality of adhesive patches from the skin region in a manner sufficient to retain the adhered skin sample cells to each of the adhesive patches. 
     
     
         7 . The method of  claim 1 , wherein the skin region comprises a skin lesion. 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 1 , further comprising administering a CTCL treatment to the subject based on the sample score. 
     
     
         10 . The method of  claim 9 , wherein the CTCL treatment comprises a steroid, interferon, chemotherapy, phototherapy, radiation therapy, or a bone marrow transplant. 
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein the CTCL comprises mycosis fungoides. 
     
     
         13 . The method of  claim 1 , wherein the CTCL comprises Sézary syndrome. 
     
     
         14 .- 16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein the panel of target genes comprises a gene encoding a saposin-like protein, a gene encoding a FYN-binding protein family member, a gene encoding a TEC kinase family member, a gene encoding a STAT, a gene encoding a TRAF3 interacting protein, a gene encoding a CXC chemokine family member, or a combination thereof. 
     
     
         18 . The method of  claim 1 , wherein the panel of target genes comprises a gene encoding a modulator of cell death, a gene encoding an antimicrobial, a gene encoding a cytokine, or a gene encoding a DNA-binding protein, or a combination thereof. 
     
     
         19 . A method of treating a subject with cutaneous T cell lymphoma (CTCL), comprising:
 a. identifying a subject suspected of having CTCL;   b. isolating nucleic acids from a skin sample obtained from the subject by applying an adhesive patch to a skin region of the subject in a manner sufficient to adhere skin sample cells to the adhesive patch, and removing the adhesive patch from the skin region in a manner sufficient to retain the adhered skin sample cells to the adhesive patch, wherein the skin sample cells comprise cells from the stratum corneum;   c. measuring or detecting an expression level of at least one target gene known to be upregulated or downregulated in subjects with CTCL by:
 contacting the isolated nucleic acids with a set of probes that recognize the target gene; and 
 measuring or detecting binding between the at least one target gene and the set of probes; 
   d. determining whether the subject has CTCL based on the expression level of the at least one target gene; and   e. administering a CTCL treatment to the subject when the subject is determined to have CTCL based on the expression level of the at least one target gene, and not administering the CTCL treatment to the subject when the subject is not determined to have CTCL based on the expression level of the at least one target gene.   
     
     
         20 . A kit for determining the presence of cutaneous T cell lymphoma (CTCL) in a skin sample, comprising:
 a. an adhesive patch comprising an adhesive matrix configured to adhere skin sample cells from the stratum corneum of a subject;   b. a nucleic acid isolation reagent; and   c. a plurality of probes that recognize at least one target gene known to be upregulated or downregulated in subjects with CTCL.   
     
     
         21 . The method of  claim 1 , wherein the panel of target genes comprises at least three target genes. 
     
     
         22 . The method of  claim 21 , wherein the at least three target genes comprises at least one gene selected from the group consisting of: FYB, GNLY, ITK, STAT5, TRAF3IP3, CXCL10, CXCL8, TNF, IL26, DNM3, and TNFSF11. 
     
     
         23 . The method of  claim 21 , wherein the at least three target genes comprises at least three genes selected from the group consisting of: FYB, GNLY, ITK, STAT5, TRAF3IP3, CXCL10, CXCL8, TNF, IL26, DNM3, and TNFSF11. 
     
     
         24 . The method of  claim 1 , wherein step (b) further comprises detecting a mutational change of one or more other target genes; and step (c) further comprises using the software program or module to evaluate the mutational change to determine the skin sample gene expression signature. 
     
     
         25 . The method of  claim 24 , wherein step (c) further comprises using the software program or module to evaluate the mutational change to determine the skin sample gene expression signature. 
     
     
         26 . The method of  claim 24 , wherein the one or more other target genes are selected from the group consisting of TP53, ZEB1, ARID1A, DNMT3A, CDKN2A, FAS, STAT5B, PRKCQ, RHOA, DNMT3A, PLCG1, and NFKB2. 
     
     
         27 . The method of  claim 1 , wherein the software program or module evaluates the gene expression levels by applying a random forest model, a boosting model, a logit model, a lasso model, or a combination thereof.