CHARACTERIZATION OF MELANOMA USING A MOLECULAR SIGNATURE
The present disclosure provides methods for characterizing melanoma in a subject by analyzing genes or gene expression products obtained from the subject. The present disclosure provides methods for distinguishing melanoma in situ from invasive melanoma. The disclosure includes non-invasive methods for obtaining genes or gene expression products from a pigmented skin lesion of a subject.
1 - 110 . (canceled)
111 . A method of distinguishing melanoma in situ from invasive melanoma in a subject in need thereof, comprising:
a) analyzing a biological sample obtained from the subject to generate an expression profile of one or more genes of a gene classifier comprising WFDC3, SLC16A6, DUSP4, PPAP2A, NDUFAF4 and BCL2A1 by applying one or more probes to gene expression products of one or more of the genes of the gene classifier in the biological sample, wherein the one or more probes comprise nucleic acid sequences specific and complementary to one or more of the genes of the gene classifier, and hybridizing the one or more probes to the gene expression products; and
b) classifying the subject as having melanoma in situ or invasive melanoma based on the expression profile, thereby distinguishing melanoma in situ from invasive melanoma.
112 . The method of claim 111 , wherein classifying in step b) further comprises comparing the expression profile of the one or more genes of the gene classifier in the biological sample to a gene expression profile of the one or more genes of the gene classifier in at least one reference sample, provided that the at least one reference sample is selected from an individual with melanoma in situ or invasive melanoma.
113 . The method of claim 111 , further comprising determining an expression profile for at least one additional gene selected from DMXL2, SMG1, SLC2A3, VEGFA, BEX4, SH3BP5, RAB27A, FEM1A, CYTH3, IRGQ, EFNA5, NAMPT, PNPT1, and HNRNPH3.
114 . The method of claim 111 , provided that the biological sample is a skin sample.
115 . The method of claim 114 , provided that the skin sample is a skin lesion sample.
116 . The method of claim 114 , provided that the skin sample is obtained by applying an adhesive tape to a target area of skin in a manner sufficient to adhere the skin sample to the adhesive tape and removing the adhesive tape from the skin in a manner sufficient to retain the adhered skin sample to the adhesive tape.
117 . The method of claim 111 , provided that the gene expression products are cDNA molecules reversely transcribed from RNA molecules expressed from the one or more genes of the gene classifier.
118 . The method of claim 111 , wherein the analyzing comprises microarray analysis, digital gene expression, a direct sequencing method or polymerase chain reaction (PCR).
119 . The method of claim 111 , further comprising providing an appropriate treatment option.
120 . The method of claim 119 , wherein the appropriate treatment option comprises biopsy, chemotherapeutic treatment, radiation treatment, anti-angiogenic compounds, or combinations thereof.
121 . A kit for distinguishing melanoma in situ from invasive melanoma in a subject in need thereof, comprising at least one primer or probe for the detection of gene expression products of one or more genes of a gene classifier comprising WFDC3, SLC16A6, DUSP4, PPAP2A, NDUFAF4 and BCL2A1.
122 . The kit of claim 121 , wherein the gene expression products are nucleic acid molecules or protein molecules.
123 . The kit of claim 122 , wherein the nucleic acid molecules are RNA molecules.
124 . The kit of claim 123 , wherein the at least one primer or probe hybridizes to one or more cDNA molecules transcribed from the RNA molecules.
125 . The kit of claim 121 , further comprising a skin sample collection device and/or a sample collector.
126 . The kit of claim 125 , provided that the skin sample collection device is an adhesive tape.
127 . A method of distinguishing melanoma in situ from invasive melanoma in a subject in need thereof and administering a treatment option to the subject, comprising:
a) analyzing a biological sample obtained from the subject to generate an expression profile of one or more genes of a gene classifier comprising WFDC3, SLC16A6, DUSP4, PPAP2A, NDUFAF4 and BCL2A1;
b) classifying the subject as having melanoma in situ or invasive melanoma based on the expression profile, thereby distinguishing melanoma in situ from invasive melanoma; and
c) based on step b), administering an appropriate treatment option to the subject, wherein the appropriate treatment option is a treatment for melanoma in situ or a treatment for invasive melanoma.
128 . The method of claim 127 , wherein classifying in step b) further comprises comparing the expression profile of the one or more genes of the gene classifier in the biological sample to a gene expression profile of the one or more genes of the gene classifier in at least one reference sample, provided that the at least one reference sample is selected from an individual with melanoma in situ or invasive melanoma.
129 . The method of claim 127 , wherein the analyzing further comprises:
a) applying one or more probes to gene expression products expressed from the one or more genes of the gene classifier; provided that the one or more probes comprise nucleic acid sequences specific and complementary to one or more of the genes of the gene classifier; and
b) hybridizing the one or more probes to the gene expression products.
130 . The method of claim 127 , wherein the analyzing further comprises microarray analysis, digital gene expression, a direct sequencing method or polymerase chain reaction (PCR).