Use of DNA in circulating exosomes as a diagnostic marker for metastatic disease
The present invention is directed to methods of diagnosing, prognosing, and monitoring cancer in a subject. These methods involves selecting a subject having cancer, and obtaining, from the selected subject, a sample containing exosomal DNA. The presence or absence of one or more mutations in BRAF and/or EGFR is detected in the exosomal DNA sample from the subject, and a diagnosis and/or prognosis of the cancer is given based on the detection of the one or more mutations in BRAF and/or EGFR. The present invention further relates to methods of treating a subject having cancer and/or monitoring a subject response to therapy based on the detection of one or more mutations in BRAF and/or EGFR in the exosomal DNA sample.
1. A method comprising:
selecting a subject having cancer;
obtaining, from the selected subject, a sample containing exosomes;
isolating whole genomic DNA from the exosomes in the sample;
sequencing the isolated exosome derived whole genomic DNA;
and
detecting the presence or absence of the one or more genetic mutations in the exosome derived whole genomic DNA from the sample based on said sequencing to genotype the cancer of the subject.
2. The method of claim 1 further comprising:
selecting a suitable cancer therapeutic based on said detecting and
administering the selected cancer therapeutic to said selected subject.
3. The method of claim 1 , wherein the cancer is selected from the group consisting of melanoma, breast cancer, brain cancer, pancreatic cancer, ovarian cancer, colorectal cancer, liver cancer, renal cancer, prostate cancer, and lung cancer.
4. The method of claim 1 , wherein the selected subject has melanoma and the presence or absence of a mutation in BRAF is detected.
5. The method of claim 4 , wherein the detection of a mutation in BRAF is the detection of the presence of a V600E BRAF mutation.
6. The method of claim 1 , wherein the one or more detected genetic mutations are in EGFR and are selected from the group consisting of an exon 19 deletion, L858R, T790M, and any combination thereof.