A Molecular Diagnostic Assay for Accurately Differentiating Melanoma from Benign Lesions

AbstractMelanoma is the third most common form of skin cancer with estimatednew cases diagnosed in the United States in the yearCurrent routine diagnostic approaches utilize microscopic evaluation of thinly sectioned patient biopsiesbut in certain cases diagnosis can be contentious even among expertsThe overall goal of this multi phase SBIR project is to developvalidateand commercialize MelanoMapTMFrontier Diagnosticsandapospatented assay for the diagnosis of melanoma using a matrix assisted laser desorption ionization imaging mass spectrometryMALDI IMSplatform and to have this assay available to pathologists in the U Sas a laboratory developed testMALDI IMS is a state of the art technology that generates molecular images of tens to thousands of biomolecules from tissue sections in a single analysisThe assay uses formalin fixed paraffin embeddedFFPEbiopsies used in routine histopathological diagnosisThe proposed assay has pathologists select regions of skin biopsies for analysis via a remote web interfaceThe acquired IMS data from those regions unambiguously identifies malignant melanoma or benign nevusPhase I of this proposal will demonstrate the feasibility of this technology platform to achieve cost effective diagnosis of melanoma from patient skin biopsies at sample volumes acceptable for a clinical laboratorySpecific Aimfocuses on the development of a scalable and robust analytical protocol in both sample preparation and informatics to accurately diagnose melanoma with MALDI IMSIn specific aimwe will test the methodology developed in Specific Aimon a cohort of melanocytic lesions with known clinical outcome and subsequently validate the classification accuracy of the proposed testIn Phase IIthe protocols developed in Phase I will be integrated into a diagnostic service workflowThis phase will focus on quality control measuresclient facing cloud softwareclinical diagnostic reportingand completing the analysis of apatient sample set for final assay validationSpecific Aimof this proposalinitial aim of Phase IIwill establish and implement test tissues into standard workflows that will provide performance metrics for standard operation of a test meeting Clinical Laboratory Improvement AmendmentsCLIAstandardsProtocols will be developed to monitor reagentsthe reproducibility of sample preparationand mass spectrometer performance on daily basisSpecific Aimwill expand software capabilities to include a secure web interface for clients ordering the test and the laboratory performing the testThe software will meet regulatory complianceperform statistical analysisand generate and communicate reports of the MALDI IMS analysisSpecific Aimproposes to expand the sample set used in the initial assay from Specific Aimto include a set ofpatient samples from our clinical collaborators withor more years follow up dataThe test will be independently validated by an additionalpatient samples with definitive diagnoses Project Narrative This multi phase Fast Track SBIR project will develop and validate a new laboratory developed test to differentiate malignant melanocytic tumors from benign nevi and complete development of an imaging mass spectrometry based diagnostic service platform for a clinical laboratoryThe clinical assay developed under this proposal augments current practice by providing molecular measurements that are used as objective criteria in the diagnosis of melanomaSuccessful completion of this Fast Track project will result in a fully documented and validated assay ready for launch as a laboratory developed test