title: Point of care assessment of melanoma tumor signaling and metastatic burden from μNMR analysis of tumor fine needle aspirates and peripheral blood.
abstract: This study evaluates μNMR technology for molecular profiling of tumor fine needle aspirates and peripheral blood of melanoma patients. In vitro assessment of melanocyte (MART-1, HMB45) and MAP kinase signaling (pERK, pS6K) molecule expression was performed in human cell lines, while clinical validation was performed in an IRB-approved study of melanoma patients undergoing biopsy and blood sampling. Tumor FNA and blood specimens were compared with BRAF genetic analysis and cross-sectional imaging. μNMR in vitro analysis showed increased expression of melanocyte markers in melanoma cells as well as increased expression of phosphorylated MAP kinase targets in BRAF-mutant melanoma cells. Melanoma patient FNA samples showed increased pERK and pS6K levels in BRAF mutant compared with BRAF WT melanomas, with μNMR blood circulating tumor cell level increased with higher metastatic burden visible on imaging. These results indicate that μNMR technology provides minimally invasive point-of-care evaluation of tumor signaling and metastatic burden in melanoma patients.
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Boston, MA 02114.|Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gee
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114.
authors.forename: Arezou A
authors.initials: AA
authors.lastname: Ghazani
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Boston, MA 02114.
authors.forename: Rizwan
authors.initials: R
authors.lastname: Haq
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Boston, MA 02114.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Wargo
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114.
authors.forename: Matthew
authors.initials: M
authors.lastname: Sebas
authors.affiliation: Center for Melanoma, Massachusetts General Hospital Cancer Center, Boston, MA 02114.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Sullivan
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114.
authors.forename: Hakho
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Boston, MA 02114.|Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114.
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
mesh_terms: D044963:Biopsy, Fine-Needle / Q000379:methods; D045744:Cell Line, Tumor; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology*; D008545:Melanoma / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D019095:Point-of-Care Systems; D048493:Proto-Oncogene Proteins B-raf / Q000032:analysis / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D048493:Proto-Oncogene Proteins B-raf; D020928:Mitogen-Activated Protein Kinases
keywords: Biopsy; Circulating tumor cells; Melanoma; Treatment response