The MM500 meta‐study aims to establish a knowledge basis of the tumor proteome to
serve as a complement to genome and transcriptome studies. Somatic mutations and their
effect on the transcriptome have been extensively characterized in melanoma. However,
the effects of these genetic changes on the proteomic landscape and the impact on
cellular processes in melanoma remain poorly understood. In this study, the quantitative
mass‐spectrometry‐based proteomic analysis is interfaced with pathological tumor characterization,
and associated with clinical data. The melanoma proteome landscape, obtained by the
analysis of 505 well‐annotated melanoma tumor samples, is defined based on almost
16 000 proteins, including mutated proteoforms of driver genes. More than 50 million
MS/MS spectra were analyzed, resulting in approximately 13,6 million peptide spectrum
matches (PSMs). Altogether 13 176 protein‐coding genes, represented by 366 172 peptides,
in addition to 52 000 phosphorylation sites, and 4 400 acetylation sites were successfully
annotated. This data covers 65% and 74% of the predicted and identified human proteome,
respectively. A high degree of correlation (Pearson, up to 0.54) with the melanoma
transcriptome of the TCGA repository, with an overlap of 12 751 gene products, was
found.Mapping of the expressed proteins with quantitation, spatiotemporal
localization, mutations, splice isoforms, and PTM variants was proven not to be predicted
by genome sequencing alone. The melanoma tumor molecular map was complemented by analysis
of blood protein expression, including data on proteins regulated after immunotherapy.
By adding these key proteomic pillars, the MM500 study expands the knowledge on melanoma
disease.
