Proteomic analysis and classification of metastatic melanoma by MALDI imaging mass spectrometry

Abstract

CHEMISTRY

PROTEOMIC ANALYSIS AND CLASSIFICATION OF METASTATIC MELANOMA BY MALDI IMAGING MASS SPECTROMETRY

WILLIAM MICHAEL HARDESTY

Dissertation under the direction of Professor Richard M. Caprioli

Classification of malignant melanoma from protein signatures is presented. Protein signals were acquired directly from thin sections of human melanoma, control lymph node, and skin biopsies using matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry. First, protein spectra collected from 62 fresh-frozen stage III melanomas are distinguished from cancer-free control lymph nodes and used to categorize patients into poor and favorable prognostic groups. Secondly, MALDI imaging is applied to two formalin-fixed tissue microarrays which showed trends in collagen and histone levels in progression from primary to metastatic disease. Proteins are identified by purification followed by enzymatic digestion as well as by direct fragmentation.